scholarly journals Plasma cell S1P1 expression determines secondary lymphoid organ retention versus bone marrow tropism

2006 ◽  
Vol 203 (12) ◽  
pp. 2683-2690 ◽  
Author(s):  
Kenji Kabashima ◽  
Nicole M. Haynes ◽  
Ying Xu ◽  
Stephen L. Nutt ◽  
Maria L. Allende ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Lymphoid Organ ◽  
Lymphoid Organs ◽  
Secondary Response ◽  
Secondary Lymphoid Organ ◽  
Lower Blood ◽  
Sphingosine 1 Phosphate ◽  
Secondary Lymphoid Organs

After induction in secondary lymphoid organs, a subset of antibody-secreting cells (ASCs) homes to the bone marrow (BM) and contributes to long-term antibody production. The factors determining secondary lymphoid organ residence versus BM tropism have been unclear. Here we demonstrate that in mice treated with FTY720 or that lack sphingosine-1-phosphate (S1P) receptor-1 (S1P1) in B cells, IgG ASCs are induced and localize normally in secondary lymphoid organs but they are reduced in numbers in blood and BM. Many IgG ASCs home to BM on day 3 of the secondary response and day 3 splenic ASCs exhibit S1P responsiveness, whereas the cells remaining at day 5 are unable to respond. S1P1 mRNA abundance is higher in ASCs isolated from blood compared to spleen, whereas CXCR4 expression is lower. Blood ASCs also express higher amounts of Kruppel-like factor (KLF)2, a regulator of S1P1 gene expression. These findings establish an essential role for S1P1 in IgG plasma cell homing and they suggest that differential regulation of S1P1 expression in differentiating plasma cells may determine whether they remain in secondary lymphoid organs or home to BM.

scholarly journals A Coordinated Change in Chemokine Responsiveness Guides Plasma Cell Movements

2001 ◽  
Vol 194 (1) ◽  
pp. 45-56 ◽  
Author(s):  
Diana C. Hargreaves ◽  
Paul L. Hyman ◽  
Theresa T. Lu ◽  
Vu N. Ngo ◽  
Afshin Bidgol ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Fetal Liver ◽  
B Cell Precursors ◽  
Secondary Lymphoid Organs ◽  
Splenic Red Pulp ◽  
Medullary Cords ◽  
Red Pulp

Antibody-secreting plasma cells are nonrecirculatory and lodge in splenic red pulp, lymph node medullary cords, and bone marrow. The factors that regulate plasma cell localization are poorly defined. Here we demonstrate that, compared with their B cell precursors, plasma cells exhibit increased chemotactic sensitivity to the CXCR4 ligand CXCL12. At the same time, they downregulate CXCR5 and CCR7 and have reduced responsiveness to the B and T zone chemokines CXCL13, CCL19, and CCL21. We demonstrate that CXCL12 is expressed within splenic red pulp and lymph node medullary cords as well as in bone marrow. In chimeric mice reconstituted with CXCR4-deficient fetal liver cells, plasma cells are mislocalized in the spleen, found in elevated numbers in blood, and fail to accumulate normally in the bone marrow. Our findings indicate that as B cells differentiate into plasma cells they undergo a coordinated change in chemokine responsiveness that regulates their movements in secondary lymphoid organs and promotes lodgment within the bone marrow.

scholarly journals Characterization of B and plasma cells in blood, bone marrow, and secondary lymphoid organs of rhesus macaques by multicolor flow cytometry

2014 ◽  
Vol 97 (1) ◽  
pp. 19-30 ◽  
Author(s):  
Berit Neumann ◽  
Antonina Klippert ◽  
Katharina Raue ◽  
Sieghart Sopper ◽  
Christiane Stahl-Hennig
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Plasma Cells ◽  
Rhesus Macaques ◽  
Lymphoid Organs ◽  
Multicolor Flow Cytometry ◽  
Secondary Lymphoid Organs

scholarly journals Cooperating Mechanisms of CXCR5 and CCR7 in Development and Organization of Secondary Lymphoid Organs

2003 ◽  
Vol 197 (9) ◽  
pp. 1199-1204 ◽  
Author(s):  
Lars Ohl ◽  
Golo Henning ◽  
Stefan Krautwald ◽  
Martin Lipp ◽  
Svenja Hardtke ◽  
...  
Keyword(s):  
Functional Organization ◽  
Mesenchymal Cells ◽  
Lymphoid Organ ◽  
Lymphoid Organs ◽  
White Pulp ◽  
Organ Development ◽  
Secondary Lymphoid Organ ◽  
Small Clusters ◽  
Secondary Lymphoid Organs ◽  
Deficient Mice

Homeostatic chemokines participate in the development of secondary lymphoid organs and later on in the functional organization of these tissues. The development of lymph nodes (LNs) and Peyer's patches depends on the recruitment of CD3− CD4+ interleukin (IL)-7Rαhi cells to sites of future organ development. CD3− CD4+ IL-7Rαhi cells express the chemokine receptor CXCR5 and might be attracted by its ligand CXCL13, which is secreted by mesenchymal cells. Mesenchymal cells also secrete CCL19, a ligand for CCR7, yet it is not clear whether CCR7 and CCL19 are important for secondary lymphoid organ development. Analyzing CXCR5−/− CCR7−/− double deficient mice we now show that these mice lack all examined peripheral LNs suggesting a profound role for both receptors in secondary lymphoid organ development. We demonstrate that CD3− CD4+ IL-7Rαhi cells express CXCR5 as well as CCR7 indicating that both receptors cooperate during an early step of secondary lymphoid organ development. Furthermore, CXCR5−/− CCR7−/− mice display a severely disturbed architecture of mesenteric LN and spleen. Due to an impaired migration of B cells into the white pulp, CXCR5−/− CCR7−/− mice fail to develop B cell follicles but show small clusters of unorganized lymphocytes in the spleen. These data demonstrate a cooperative function of CXCR5 and CCR7 in lymphoid organ organogenesis and organization.

Generation of migratory antigen-specific plasma blasts and mobilization of resident plasma cells in a secondary immune response

Blood ◽  
2005 ◽  
Vol 105 (4) ◽  
pp. 1614-1621 ◽  
Author(s):  
Marcus Odendahl ◽  
Henrik Mei ◽  
Bimba F. Hoyer ◽  
Annett M. Jacobi ◽  
Arne Hansen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Responses ◽  
Tetanus Toxin ◽  
Plasma Cells ◽  
Lymphoid Organs ◽  
Term Survival ◽  
Large Numbers ◽  
Secondary Lymphoid Organs ◽  
Antibody Secreting Cells

AbstractMaintenance of protective humoral immunity depends on the generation and survival of antibody-secreting cells. The bone marrow provides niches for long-term survival of plasma cells generated in the course of systemic immune responses in secondary lymphoid organs. Here, we have analyzed migratory human plasma blasts and plasma cells after secondary vaccination with tetanus toxin. On days 6 and 7 after immunization, CD19+/CD27high/intracellular immunoglobulin Ghigh (IgGhigh)/HLA-DRhigh/CD38high/CD20–/CD95+ tetanus toxin–specific antibody-secreting plasma blasts were released in large numbers from the secondary lymphoid organs into the blood. These cells show chemotactic responsiveness toward ligands for CXCR3 and CXCR4, probably guiding them to the bone marrow or inflamed tissue. At the same time, a population of CD19+/CD27high/intracellular IgGhigh/HLA-DRlow/CD38+/CD20–/CD95+ cells appeared in the blood in large numbers. These cells, with the phenotype of long-lived plasma cells, secreted antibodies of unknown specificity, not tetanus toxoid. The appearance of these plasma cells in the blood indicates successful competition for survival niches in the bone marrow between newly generated plasma blasts and resident plasma cells as a fundamental mechanism for the establishment of humoral memory and its plasticity.

Should CD138 Immunohistochemistry be Standard Recommended Practice for Bone Marrow Evaluation of Plasma Cell Neoplasms?

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S110-S110
Author(s):  
A Vijayanarayanan ◽  
K Inamdar ◽  
M Menon ◽  
P Kuriakose
Keyword(s):  
Bone Marrow ◽  
Plasma Cell ◽  
Linear Correlation ◽  
Plasma Cells ◽  
Pearson Correlation ◽  
Protein Electrophoresis ◽  
Pearson Correlation Coefficient ◽  
Cell Percentage ◽  
Significant Linear Correlation ◽  
Plasma Cell Neoplasms

Abstract Introduction/Objective Myeloma diagnosis by a pathologist requires 10% plasma cells (PC) or a biopsy proven plasmacytoma in addition to myeloma defining events. PC% > 60% is a biomarker of malignancy under this definition. WHO allows for assesment of plasma cell percentage either by aspirate count or by CD138 immunohistochemistry (IHC). There is lack of consensus on aspirate smear adequacy for PC% estimation. Uneven distribution of plasma cells, hemodilution and/or patchy infiltration can lead to gross underestimation. We compared PC% by aspirate count and CD138 IHC and established corelation with serum protein electrophoresis (SPEP) values. Methods 67 myeloma cases were included after excluding cases with suboptimal or inadequate aspirate smears. Two hematopathologists evaluated the diagnostic marrow (therapy naive) for PC% by aspirate count and CD138 IHC on biopsy/clot section. Corresponding SPEP and Free light chain (FLC) values were obtained. Correlation coefficent was calculated using Pearson correlation coefficient (GraphPad Prism). Results The Ig subtypes included IgG (41/67) and IgA (17/67). 12 cases had available FLC values. Both average and median PC% by CD138 IHC was considerably higher (50%, 52%) compared to aspirate count (29%, 21%). However, PC% by aspirate smear count and CD138 IHC demonstrated a significant linear correlation (r=0.71, p60% by CD138 (and not by aspirate count). Conclusion CD138 IHC based PC% is consistently higher, nevertheless, statistically significant linear corelation is observed between aspirate count PC% and CD138 IHC. A significant linear correlation is observed between CD138 IHC and SPEP (IgG and IgA), however, no such correlation is observed with aspirate count. More cases were diagnosed as myeloma (11%) and higher propotion of cases (35%) had biomarker of malignancy i.e. PC% >60% by CD138 IHC. Based on these findings, we propose estimation of PC% by CD138 immunostain be a recommended standard practice for better clinicopathologic and biologic correlation.

Diversity, localization and (patho)physiology of mature lymphocyte populations in the bone marrow

Blood ◽  
2021 ◽  
Author(s):  
Christian M. Schürch ◽  
Chiara Caraccio ◽  
Martijn A. Nolte
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Plasma Cells ◽  
Cell Types ◽  
Lymphoid Organ ◽  
Lymphoid Cells ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Mature Lymphocyte ◽  
Lymphocyte Populations

The bone marrow (BM) is responsible for generating and maintaining lifelong output of blood and immune cells. Besides its key hematopoietic function, the BM acts as an important lymphoid organ, hosting a large variety of mature lymphocyte populations, including B-cells, T-cells, NK(T)-cells and innate lymphoid cells (ILCs). Many of these cell types are thought to only transiently visit the BM, but for others, like plasma cells and memory T-cells, the BM provides supportive niches that promote their long-term survival. Interestingly, accumulating evidence points towards an important role for mature lymphocytes in the regulation of hematopoietic stem cells (HSCs) and hematopoiesis in health and disease. In this review, we describe the diversity, migration, localization and function of mature lymphocyte populations in murine and human BM, focusing on their role in immunity and hematopoiesis. We also address how various BM lymphocyte subsets contribute to the development of aplastic anemia and immune thrombocytopenia, illustrating the complexity of these BM disorders, but also the underlying similarities and differences in their disease pathophysiology. Finally, we summarize the interactions between mature lymphocytes and BM resident cells in HSC transplantation and graft-versus-host disease. A better understanding of the mechanisms by which mature lymphocyte populations regulate BM function will likely improve future therapies for patients with benign and malignant hematological disorders.

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