Role of Natural IgM Autoantibodies (IgM-NAA) and IgM Anti-Leukocyte Antibodies (IgM-ALA) in Regulating Inflammation

2017 ◽  
pp. 89-117
Author(s):  
Peter I. Lobo
Keyword(s):  
Natural Igm

THE ROLE OF NATURAL IgM IN THE HYPERACUTE REJECTION OF DISCORDANT HEART XENOGRAFTS

1992 ◽  
Vol 54 (4) ◽  
pp. 577-582 ◽  
Author(s):  
LUC GAMBIEZ ◽  
EPHREM SALAME ◽  
CHRISTIANS CHEREAU ◽  
YVON CALMUS ◽  
JORGE CARDOSO ◽  
...  
Keyword(s):  
Hyperacute Rejection ◽  
Natural Igm

scholarly journals Critical role of IL-25-ILC2-IL-5 axis in the production of anti-Francisella LPS IgM by B1 B cells

2021 ◽  
Vol 17 (8) ◽  
pp. e1009905
Author(s):  
Carlos Henrique D. Barbosa ◽  
Louis Lantier ◽  
Joseph Reynolds ◽  
Jinyong Wang ◽  
Fabio Re
Keyword(s):  
Critical Role ◽  
Negative Bacterium ◽  
Adaptive Immune ◽  
Secondary Challenge ◽  
And Function ◽  
B1 Cells ◽  
Natural Igm ◽  
Antibody Secreting Cells ◽  
Stimulation Of

B1 cells, a subset of B lymphocytes whose developmental origin, phenotype, and function differ from that of conventional B2 cells, are the main source of “natural” IgM but can also respond to infection by rapidly producing pathogen-specific IgM directed against T-independent antigens. Francisella tularensis (Ft) is a Gram-negative bacterium that causes tularemia. Infection with Ft Live Vaccine Strain activates B1 cells for production of IgM directed against the bacterial LPS in a process incompletely understood. Here we show that immunization with purified Ft LPS elicits production of LPS-specific IgM and IgG3 by B1 cells independently of TLR2 or MyD88. Immunization, but not infection, generated peritoneum-resident memory B1 cells that differentiated into LPS-specific antibody secreting cells (ASC) upon secondary challenge. IL-5 was rapidly induced by immunization with Ft LPS and was required for production of LPS-specific IgM. Antibody-mediated depletion of ILC2 indicated that these cells were the source of IL-5 and were required for IgM production. IL-25, an alarmin that strongly activates ILC2, was rapidly secreted in response to immunization or infection and its administration to mice significantly increased IgM production and B1 cell differentiation to ASC. Conversely, mice lacking IL-17RB, the IL-25 receptor, showed impaired IL-5 induction, IgM production, and B1 ASC differentiation in response to immunization. Administration of IL-5 to Il17rb-/- mice rescued these B1 cells-mediated responses. Il17rb-/- mice were more susceptible to infection with Ft LVS and failed to develop immunity upon secondary challenge suggesting that LPS-specific IgM is one of the protective adaptive immune mechanisms against tularemia. Our results indicated that immunization with Ft LPS triggers production of IL-25 that, through stimulation of IL-5 release by ILC2, promotes B1 cells activation and differentiation into IgM secreting cells. By revealing the existence of an IL-25-ILC2-IL-5 axis our results suggest novel strategies to improve vaccination against T-independent bacterial antigens.

scholarly journals X-linked immunodeficient (XID) mice exhibit high susceptibility to Cryptococcus gattii infection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Israel Diniz-Lima ◽  
Pablo Rodrigo da Rosa ◽  
Elias Barbosa da Silva-Junior ◽  
Joyce Cristina Guimarães-de-Oliveira ◽  
Elisangela Oliveira de Freitas ◽  
...  
Keyword(s):  
Pulmonary Infection ◽  
Fungal Infections ◽  
Humoral Response ◽  
Cryptococcus Gattii ◽  
Opportunistic Disease ◽  
Fungal Load ◽  
Natural Igm ◽  
The Brain ◽  
Chronic Lung Infection

AbstractCryptococcosis is an opportunistic disease caused by the fungus Cryptococcus neoformans and Cryptococcus gattii. It starts as a pulmonary infection that can spread to other organs, such as the brain, leading to the most serious occurrence of the disease, meningoencephalitis. The humoral response has already been described in limiting the progression of cryptococcosis where the B-1 cell seems to be responsible for producing natural IgM antibodies, crucial for combating fungal infections. The role of the B-1 cell in C. neoformans infection has been initially described, however the role of the humoral response of B-1 cells has not yet been evaluated during C. gattii infections. In the present study we tried to unravel this issue using XID mice, a murine model deficient in the Btk protein which compromises the development of B-1 lymphocytes. We use the XID mice compared to BALB/c mice that are sufficient for the B-1 population during C. gattii infection. Our model of chronic lung infection revealed that XID mice, unlike the sufficient group of B-1, had early mortality with significant weight loss, in addition to reduced levels of IgM and IgG specific to GXM isolated from the capsule of C. neoformans. In addition to this, we observed an increased fungal load in the blood and in the brain. We described an increase in the capsular size of C. gattii and the predominant presence of cytokines with a Th2 profile was also observed in these animals. Thus, the present study strongly points to a higher susceptibility of the XID mouse to C. gattii, which suggests that the presence of B-1 cells and anti-GXM antibodies is fundamental during the control of infection by C. gattii.

Immunodeficient Mice Are Poor Mobilizers -Novel Evidence That Demonstrates a Pivotal Role of Complement in Triggering Mobilization of HSPC.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1976-1976 ◽  
Author(s):  
Ryan Reca ◽  
Marcin Wysoczynski ◽  
Richard Hansen ◽  
Magda Kucia ◽  
Anna Janowska-Wieczorek ◽  
...  
Keyword(s):  
B Lymphocytes ◽  
Alternative Pathway ◽  
Normal Serum ◽  
Wild Type ◽  
Hematopoietic Stem ◽  
Alternative Pathways ◽  
Immunodeficient Mice ◽  
Natural Igm ◽  
Dependent Pathway

Abstract Complement (C) is activated by immunoglobulin-dependent classical and immunoglobulin-independent alternative pathways, and we recently reported that the activation of C enhances the responsiveness of hematopoietic stem/progenitor cells (HSPC) to an SDF-1 gradient cascade by releasing C3a and desArgC3a cleavage fragments (Blood2003;101:3784; Blood2004; 103: 2071). We also found that bone marrow (BM) concentration of C3a and desArgC3a increases during mobilization with G-CSF or cyclophosphamide (CY). To explain this phenomenon we envisioned that these mobilizing agents expose a neo-antigen in BM tissue by turning BM into a highly proteolytic microenvironment. As a consequence of this, the newly exposed neo-epitope becomes bound by natural IgM antibodies leading to the activation of the classical C cascade. In our studies to elucidate the role of C activation in triggering the mobilization of HSPC, we found that C is effectively activated in the BM of G-CSF- or CY- mobilized wild-type (wt) but not IgM-deficient (RAG2null) mice. More importantly we found that several immunodeficient murine strains (RAG2null, SCID and Xid) displayed severely reduced G-CSF-induced mobilization of HSPC which we believe is a result of lack of B lymphocytes and complement-activating immunoglobulins. Supporting this, we found T cell depletion in wt mice did not affect mobilization. Moreover, G-CSF-induced mobilization in RAG2null, SCID and Xid animals was restored after infusion of murine inmmunoglobulins. Furthermore, since mobilization by zymosan or sulfated glycans activates C via the alternative immunoglobulin-independent pathway, we focused on the role of C activation during zymosan-induced mobilization. As expected, zymosan-induced immunoglobulin-independent C activation and mobilization of HSPC were unaffected in immunodeficient (RAG2null, SCID and Xid) mice which have a normal serum level of C3. However, these processes were severely reduced in C3-deficient animals. Thus our data strongly support the notion that C and innate immunity is an important trigger of mobilization of HSPC. While G-CSF and cyclophosphamide activate C by a classical IgM-dependent pathway, zymosan and sulfated polyglycans activate it by employing an alternative pathway. In conclusion, mobilization of HSPC could be envisioned as part of a more global immune response that is triggered/mediated by C3 activation/cleavage.

The role of natural IgM in myocardial ischemia–reperfusion injury

2006 ◽  
Vol 41 (1) ◽  
pp. 62-67 ◽  
Author(s):  
Ming Zhang ◽  
Lloyd H. Michael ◽  
Sandrine A. Grosjean ◽  
Ralph A. Kelly ◽  
Michael C. Carroll ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Natural Igm

Protective Role of Natural IgM-Producing B1a Cells in Atherosclerosis

2012 ◽  
Vol 22 (2) ◽  
pp. 48-53 ◽  
Author(s):  
Tin Kyaw ◽  
Peter Tipping ◽  
Alex Bobik ◽  
Ban-Hock Toh
Keyword(s):  
Protective Role ◽  
B1a Cells ◽  
Natural Igm

scholarly journals B-1 and B-2 Cell–Derived Immunoglobulin M Antibodies Are Nonredundant Components of the Protective Response to Influenza Virus Infection

2000 ◽  
Vol 192 (2) ◽  
pp. 271-280 ◽  
Author(s):  
Nicole Baumgarth ◽  
Ometa C. Herman ◽  
Gina C. Jager ◽  
Lorena E. Brown ◽  
Leonore A. Herzenberg ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Survival Rates ◽  
Influenza Virus Infection ◽  
Serum Levels ◽  
Immunoglobulin M ◽  
Virus Clearance ◽  
Efficient Induction ◽  
Specific Igg ◽  
Natural Igm

We have studied the role of secreted immunoglobulin (Ig)M in protection from infection with influenza virus and delineated the relative contributions of B-1 versus B-2 cell–derived IgM in this process. Mice deficient in secreted IgM but capable of expressing surface IgM and secreting other Ig classes show significantly reduced virus clearance and survival rates compared with wild-type controls. Irradiation chimeras in which only either B-1 or B-2 cells lack the ability to secrete IgM show mortality rates similar to those of mice in which neither B-1 nor B-2 cells secrete IgM. Dependence on both sources of IgM for survival is partially explained by findings in allotype chimeras that broadly cross-reactive B-1 cell–derived natural IgM is present before infection, whereas virus strain–specific, B-2 cell–derived IgM appears only after infection. Furthermore, lack of IgM secreted from one or both sources significantly impairs the antiviral IgG response. Reconstitution of chimeras lacking B-1 cell–derived IgM only with IgM-containing serum from noninfected mice improved both survival rates and serum levels of virus-specific IgG. Thus, virus-induced IgM must be secreted in the presence of natural IgM for efficient induction of specific IgG and for immune protection, identifying B-1 and B-2 cell–derived IgM antibodies as nonredundant components of the antiviral response.

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