scholarly journals Anatomically remote education of B cells is required for colonic health

2019 ◽  
Author(s):  
Neeraj K. Surana ◽  
Cheryn J. Couter ◽  
David Alvarez ◽  
Uli H. von Andrian ◽  
Dennis L. Kasper
Keyword(s):  
Immune System ◽  
B Cells ◽  
Plasma Cells ◽  
Lymphoid Tissues ◽  
Mucosal Tissues ◽  
Mucosal Site ◽  
Mucosal Vaccines ◽  
Small Intestinal ◽  
Colonic Health ◽  
Intestinal Lymphoid Tissue

AbstractMucosa-associated lymphoid tissues contain roughly 80% of all immune cells and produce virtually all of the body’s IgA1–3. Although the majority of IgA-secreting cells educated within a mucosal site home back to the same anatomic region, some cells are also found in distant mucosal tissues2–6. These observations underlie the notion of a common mucosal immune system, which holds that anatomically unrelated mucosal sites are functionally connected by a shared immune system2,3. However, the ontological basis of this separation between site of immune education and functionality has remained elusive. Here we show that mice lacking Peyer’s patches (PPs)—small-intestinal lymphoid tissue covered by antigen-sampling M cells—have no immunologic defect in the small-intestinal lamina propria. Surprisingly, the primary immunological abnormality in PP-deficient mice was a reduction in colonic B cells, including plasmablasts but not plasma cells. Adoptive transfer experiments conclusively demonstrated that PP-derived cells preferentially give rise to colonic—but not small-intestinal—B cells and plasmablasts. Finally, these PP-derived colonic B cells were critical for restraining colonic inflammation. Thus, PPs bridge the small-intestinal and colonic immune systems and provide a clear example of immune education being required in an anatomic compartment distinct from the effector site. Our findings, which highlight that the majority of fecal IgA is produced by colonic plasmablasts that originate from PPs, will help inform design of mucosal vaccines.

scholarly journals Altered antigen receptor signaling and impaired Fas-mediated apoptosis of B cells in Lyn-deficient mice.

1996 ◽  
Vol 184 (3) ◽  
pp. 831-838 ◽  
Author(s):  
J Wang ◽  
T Koizumi ◽  
T Watanabe
Keyword(s):  
B Cells ◽  
B Cell ◽  
Protein Tyrosine Kinase ◽  
Plasma Cells ◽  
Cell Function ◽  
Antigen Receptor ◽  
Cd40 Ligand ◽  
Lymphoid Tissues ◽  
Cd40 Ligation ◽  
Bcr Signaling

Mice deficient in the src related protein tyrosine kinase, Lyn, exhibit splenomegaly and accumulate lymphoblast-like and plasma cells in spleen as they age, resulting in elevated levels of serum IgM (10-20-fold of control) and glomerulonephritis due to the presence of immune complexes containing auto-reactive antibodies. It remains unclear, however, how antibody-producing cells are accumulated in the lymphoid tissues of Lyn-/- mice. To elucidate the role of Lyn in B cell function, we have studied the proliferative responses to various stimuli and Fas-mediated apoptosis in B cells from young Lyn-/- mice which do not yet show apparent abnormality such as splenomegaly. Compared with control B cells, Lyn-/- B cells were hyper responsive to anti-IgM-induced proliferation and defective in Fc gamma RIIB-mediated suppression of B cell antigen receptor (BCR) signaling, indicating that Lyn is involved in the negative regulation of BCR signaling. In addition, the BCR-mediated signal in Lyn-/- B cells, unlike that in control B cells, failed to act in synergy with either CD40- or IL-4 receptor-triggered signal in inducing a strong proliferative response, suggesting that the BCR signaling pathway in Lyn-/- B cells is altered from that in control B cells. Furthermore, Lyn-/- B cells were found to be impaired in the induction of Fas expression after CD40 ligation and exhibited a reduced susceptibility to Fas-mediated apoptosis. Moreover, BCR cross-linking in Lyn-/- B cells suppressed Fas expression induced by costimulation with CD40 ligand and IL-4. Collectively, these results suggest that the accumulation of lymphoblast-like and plasma cells in Lyn-/- mice may be caused in part, by the accelerated activation of B cells in the absence of Lyn, as well as the impaired Fas-mediated apoptosis after the activation.

scholarly journals LAF-4 encodes a lymphoid nuclear protein with transactivation potential that is homologous to AF-4, the gene fused to MLL in t(4;11) leukemias

Blood ◽  
1996 ◽  
Vol 87 (2) ◽  
pp. 734-745 ◽  
Author(s):  
C Ma ◽  
LM Staudt
Keyword(s):  
B Cells ◽  
Fusion Protein ◽  
Nuclear Protein ◽  
Plasma Cells ◽  
Sequence Similarity ◽  
Lymphoid Tissues ◽  
Transactivation Domain ◽  
Lymphoid Development ◽  
Mouse Tissues

A novel human gene, LAF-4, was isolated from a subtracted cDNA library that showed strong sequence similarity to AF-4, a gene that is translocated in t(4;11)(q21;q23) acute lymphoblastic leukemias (ALLs). In t(4;11) ALL, the AF-4 gene at 4q21 is translocated into the MLL locus at 11q23, resulting in the expression of an MLL/AF-4 fusion protein that is the presumptive oncoprotein. AF-4 and LAF-4 are homologous throughout their coding regions, yet neither protein is related to previously cloned genes. Human LAF-4 readily hybridized with genes in mouse and chicken, thus showing that this gene family has been highly conserved during vertebrate evolution. In mouse tissues, LAF-4 mRNA was found to be present at highest levels in lymphoid tissues, present at lower levels in brain and lung, and absent from other tissues. In human and mouse lymphoid cell lines, LAF-4 expression was highest in pre-B cells, intermediate in mature B cells, and absent in plasma cells, thus pointing to a potential regulatory role for LAF-4 in lymphoid development. Antibodies to LAF-4 showed it to be a nuclear protein that showed an uneven, granular immunofluorescence pattern. In vitro-translated LAF-4 was able to bind strongly to double-stranded DNA cellulose. Furthermore, both LAF-4 and AF-4 had domains that activated transcription strongly when fused to the GAL4 DNA-binding domain. Interestingly, the AF-4 transactivation domain is retained in the MLL/AF-4 fusion protein; thus, it may contribute to the transforming potential of the oncoprotein. Therefore, the cloning of LAF-4 has defined a new family of potential regulatory proteins that may function in lymphoid development and oncogenesis.

scholarly journals Helper T Cells in Idiopathic Membranous Nephropathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Qihan Zhao ◽  
Haoran Dai ◽  
Xianli Liu ◽  
Hanxue Jiang ◽  
Wenbin Liu ◽  
...  
Keyword(s):  
Immune System ◽  
B Cells ◽  
Membranous Nephropathy ◽  
Role Model ◽  
Plasma Cells ◽  
Treg Cells ◽  
Idiopathic Membranous Nephropathy ◽  
Th Cells ◽  
Treatment Regimens ◽  
Immune Imbalance

Idiopathic membranous nephropathy (IMN) is an autoimmune disease in which the immune system produces an antibody response to its own antigens due to impaired immune tolerance. Although antibodies are derived from plasma cells differentiated by B cells, the T-B cells also contribute a lot to the immune system. In particular, the subsets of helper T (Th) cells, including the dominant subsets such as Th2, Th17, and follicular helper T (Tfh) cells and the inferior subsets such as regulatory T (Treg) cells, shape the immune imbalance of IMN and promote the incidence and development of autoimmune responses. After reviewing the physiological knowledge of various subpopulations of Th cells and combining the existing studies on Th cells in IMN, the role model of Th cells in IMN was explained in this review. Finally, the existing clinical treatment regimens for IMN were reviewed, and the importance of the therapy for Th cells was highlighted.

scholarly journals BCL-6 protein is expressed in germinal-center B cells

Blood ◽  
1995 ◽  
Vol 86 (1) ◽  
pp. 45-53 ◽  
Author(s):  
G Cattoretti ◽  
CC Chang ◽  
K Cechova ◽  
J Zhang ◽  
BH Ye ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
Plasma Cells ◽  
Human Tumor ◽  
Immunohistochemical Analysis ◽  
Nucleotide Sequencing ◽  
Lymphoid Tissues ◽  
B Cell Differentiation ◽  
Germinal Center B Cells

Structural alterations of the 5′ noncoding region of the BCL-6 gene have been found in 40% of diffuse large cell lymphoma (DLCL) and 5% to 10% of follicular lymphomas (FL), suggesting that deregulated BCL-6 expression may play a role in lymphomagenesis. Nucleotide sequencing of BCL-6 cDNA predicted a protein containing six zinc-finger domains, suggesting that it may function as a transcription factor. Using antisera raised against N- and C-terminal BCL-6 synthetic oligopeptides in immunoprecipitation, immunoblot, and immunocytochemical assays, this study identifies the BCL-6 gene product as a 95-kD nuclear protein. Western blot analysis of human tumor cell lines representative of various hematopoietic lineages/stages of differentiation showed that the BCL-6 protein is predominantly expressed in the B-cell lineage where it was found in mature B cells. Immunohistochemical analysis of normal human lymphoid tissues indicated that BCL-6 expression is topographically restricted to germinal centers including all centroblasts and centrocytes. The BCL-6 protein was also detectable in inter- and intra-follicular CD4+ T cells, but not in other follicular components including mantle-zone B cells, plasma cells, dendritic cells, and macrophages. Immunohistochemical analysis of DLCL and FL biopsy samples showed that the BCL-6 protein is detectable in these tumors independent of the presence of BCL-6 gene rearrangements. These results indicate that the expression of the BCL-6 gene is specifically regulated during B-cell differentiation and suggest a role for BCL-6 in germinal center development or function. Because DLCL derive from germinal-center B cells, deregulated BCL-6 expression may contribute to lymphomagenesis by preventing postgerminal center differentiation.

scholarly journals B-Cell Immunophenotyping to Predict Vaccination Outcome in the Immunocompromised - A Systematic Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Annieck M. Diks ◽  
Lisanne A. Overduin ◽  
Laurens D. van Leenen ◽  
Lennert Slobbe ◽  
Hetty Jolink ◽  
...  
Keyword(s):  
Immune System ◽  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
Plasma Cells ◽  
Vaccination Schedule ◽  
Effective Measure ◽  
Critical Components ◽  
B Cell Subsets ◽  
And Function

Vaccination is the most effective measure to prevent infections in the general population. Its efficiency strongly depends on the function and composition of the immune system. If the immune system lacks critical components, patients will not be fully protected despite a completed vaccination schedule. Antigen-specific serum immunoglobulin levels are broadly used correlates of protection. These are the products of terminally differentiated B cells – plasma cells. Here we reviewed the literature on how aberrancies in B-cell composition and function influence immune responses to vaccinations. In a search through five major literature databases, 6,537 unique articles published from 2000 and onwards were identified. 75 articles were included along three major research lines: extremities of life, immunodeficiency and immunosuppression. Details of the protocol can be found in the International Prospective Register of Systematic Reviews [PROSPERO (registration number CRD42021226683)]. The majority of articles investigated immune responses in adults, in which vaccinations against pneumococci and influenza were strongly represented. Lack of baseline information was the most common reason of exclusion. Irrespective of study group, three parameters measured at baseline seemed to have a predictive value in assessing vaccine efficacy: (1) distribution of B-cell subsets (mostly a reduction in memory B cells), (2) presence of exhausted/activated B cells, or B cells with an aberrant phenotype, and (3) pre-existing immunological memory. In this review we showed how pre-immunization (baseline) knowledge of circulating B cells can be used to predict vaccination efficacy. We hope that this overview will contribute to optimizing vaccination strategies, especially in immunocompromised patients.

scholarly journals IL-21 signaling promotes early dissemination of KSHV infection in B lymphocytes

2021 ◽  
Author(s):  
Nedaa Alomari ◽  
Farizeh Aalasm ◽  
Romina Nabiee ◽  
Jesus Ramirez Castano ◽  
Jennifer Totonchy
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Plasma Cells ◽  
Cultured Cells ◽  
Host Immune System ◽  
Kshv Infection ◽  
Human Host ◽  
Early Stages ◽  
Immunological Mechanisms

AbstractKaposi’s sarcoma-associated herpesvirus (KSHV) extensively manipulates the host immune system and the cytokine milieu, and cytokines are known to influence the progression of KSHV-associated diseases. However, the precise role of cytokines in the early stages of KSHV infection remains undefined. Here, using our unique model of KSHV infection in tonsil lymphocytes, we investigate the influence of host cytokines on the establishment of KSHV infection in B cells. Our data demonstrate that KSHV manipulates the host cytokine microenvironment during early infection and susceptibility generally associated with downregulation of multiple cytokines. However, we show that IL-21 signaling promotes KSHV infection by promoting both plasma cell numbers and increasing KSHV infection in plasma cells. Our data reveal that IL-21 producing T cells, particularly Th17/Tc17 and central memory CD8+ T cells may represent immunological factors that modulate host-level susceptibility to KSHV infection. These results suggest that IL-21 plays a significant role in the early stages of KSHV infection in the human immune system and may represent a novel mechanism to be further explored in the context of preventing KSHV transmission.Author SummaryVery little is known about how KSHV is transmitted and how it initially establishes infection in a new human host and this lack of information limits our ability to prevent KSHV-associated cancers by limiting its person-to-person transmission. Saliva is thought to be the primary route of person-to-person transmission for KSHV, making the tonsil a likely first site for KSHV replication in a new human host. In particular, the tonsil is likely to be the first place KSHV is able to enter B cells, which are thought to be a major site of persistent infection. Our previous work identified plasma cells as a highly targeted cell type in early KSHV infection in cultured cells from human tonsil. In this study, we show that the human cytokine IL-21 promotes both overall KSHV infection and the establishment of infection in plasma cells. We also investigate the immunological mechanisms underlying this effect. Our results demonstrate that IL-21 and IL-21-producing cells are a novel factor that influences the initial establishment of KSHV infection in humans.

Expression of the IRTA1 receptor identifies intraepithelial and subepithelial marginal zone B cells of the mucosa-associated lymphoid tissue (MALT)

Blood ◽  
2003 ◽  
Vol 102 (10) ◽  
pp. 3684-3692 ◽  
Author(s):  
Brunangelo Falini ◽  
Enrico Tiacci ◽  
Alessandra Pucciarini ◽  
Barbara Bigerna ◽  
Julia Kurth ◽  
...  
Keyword(s):  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Cell Population ◽  
Lymphoid Tissue ◽  
Marginal Zone ◽  
Plasma Cells ◽  
Immunoglobulin Superfamily ◽  
Lymphoid Tissues ◽  
Marginal Zone B Cells

AbstractIRTA1 (immunoglobulin superfamily receptor translocation-associated 1) is a novel surface B-cell receptor related to Fc receptors, inhibitory receptor superfamily (IRS), and cell adhesion molecule (CAM) family members and we mapped for the first time its distribution in human lymphoid tissues, using newly generated specific antibodies. IRTA1 was selectively and consistently expressed by a B-cell population located underneath and within the tonsil epithelium and dome epithelium of Peyer patches (regarded as the anatomic equivalents of marginal zone). Similarly, in mucosa-associated lymphoid tissue (MALT) lymphomas IRTA1 was mainly expressed by tumor cells involved in lympho-epithelial lesions. In contrast, no or a low number of IRTA1+ cells was usually observed in the marginal zone of mesenteric lymph nodes and spleen. Interestingly, monocytoid B cells in reactive lymph nodes were strongly IRTA1+. Tonsil IRTA1+ cells expressed the memory B-cell marker CD27 but not mantle cell-, germinal center-, and plasma cell-associated molecules. Polymerase chain reaction (PCR) analysis of single tonsil IRTA1+ cells showed they represent a mixed B-cell population carrying mostly mutated, but also unmutated, IgV genes. The immunohistochemical finding in the tonsil epithelial areas of aggregates of IRTA1+ B cells closely adjacent to plasma cells surrounding small vessels suggests antigen-triggered in situ proliferation/differentiation of memory IRTA1+ cells into plasma cells. Collectively, these results suggest a role of IRTA1 in the immune function of B cells within epithelia. (Blood. 2003;102: 3684-3692)

T and B lymphocyte subpopulations

PEDIATRICS ◽  
1975 ◽  
Vol 55 (2) ◽  
pp. 157-160
Author(s):  
Robert C. Seeger ◽  
E. Richard Stiehm
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
B Lymphocyte ◽  
Plasma Cells ◽  
Cell Types ◽  
Cell System ◽  
Multiple Roles ◽  
Cellular Immune System ◽  
Cellular Immune

The two major subpopulations of lymphocytes, T cells (thymus-dependent lymphocytes) and B cells (bursal equivalent or thymus-independent lymphocytes) have multiple roles in the immune system. In general, T cells are the functioning cells in the cellular immune system (delayed hypersensitivity, graft rejection, graft-versus hostreaction); and B cells, the precursors of plasma cells which form specific antibodies, are the functioning cells in the antibody immune system. It is now well recognized, however, that these cell types and immune systems usually do not function independently, but interact with one another in multiple ways and also with other, cells such as macrophages. For example, T cells may increase or suppress the production of antibodies by the B cell system, and macrophages may increase or suppress the response of T and B cells to antigens.

scholarly journals Distribution of rotavirus-specific memory B cells in gut-associated lymphoid tissue after primary immunization

2001 ◽  
Vol 82 (9) ◽  
pp. 2271-2274 ◽  
Author(s):  
Charlotte A. Moser ◽  
Paul A. Offit
Keyword(s):  
B Cells ◽  
B Cell ◽  
Memory B Cells ◽  
Lymphoid Tissues ◽  
Memory B Cell ◽  
Cell Responses ◽  
Delayed Onset ◽  
Specific Memory ◽  
Small Intestinal ◽  
B Cell Responses

We found previously that mice inoculated orally with simian rotavirus strain RRV developed virus-specific memory B cell responses 16 weeks after immunization that were greater than those found 6 weeks after immunization. Memory B cell responses were defined as the quantity of virus-specific IgA detected in small intestinal lamina propria (LP) fragment cultures of immunized mice at various intervals after challenge. Enhanced memory B cell responses correlated with enhanced protection against shedding. In order to understand better the delayed onset of rotavirus-specific memory B cell responses, a method was developed to determine the frequencies of rotavirus-specific memory B cells in gut-associated lymphoid tissues (GALT). We found that protection against rotavirus challenge was determined by the frequency of rotavirus-specific memory B cells in GALT LP.

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