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Immunoglobulin M in Health and Diseases: How Far Have We Come and What Next? - PubMed

  • ️Wed Jan 01 2020

Review

Immunoglobulin M in Health and Diseases: How Far Have We Come and What Next?

Katelyn Jones et al. Front Immunol. 2020.

Abstract

B lymphocytes are important in secreting antibodies that protect against invading pathogens such as viruses, bacteria, parasites, and also in mediating pathogenesis of allergic diseases and autoimmunity. B lymphocytes develop in the bone marrow and contain heavy and light chains, which upon ligation form an immunoglobulin M (IgM) B cell receptor (BCR) expressed on the surface of naïve immature B cells. Naïve B cells expressing either IgM or IgD isotypes are thought to play interchangeable functions in antibody responses to T cell-dependent and T cell-independent antigens. IgM short-lived plasma cells (SLPCs) and antigen-specific IgM memory B cells (MBCs-M) are critical in the first few days of infection, as well as long-term memory induced by vaccination, respectively. At mucosal surfaces, IgM is thought to play a critical part in promoting mucosal tolerance and shaping microbiota together with IgA. In this review, we explore how IgM structure and BCR signaling shapes B cell development, self and non-self-antigen-specific antibody responses, responses to infectious (such as viruses, parasites, and fungal) and non-communicable diseases (such as autoimmunity and allergic asthma). We also explore how metabolism could influence other B cell functions such as mucosal tolerance and class switching. Finally, we discuss some of the outstanding critical research questions in both experimental and clinical settings targeting IgM.

Keywords: B cell development; immunoglobulin M (IgM); long-lived plasma cell (LLPC); memory B cell (MBC); short-lived plasma cell (SLPC).

Copyright © 2020 Jones, Savulescu, Brombacher and Hadebe.

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Figures

Figure 1
Figure 1

Immunoglobulin M (IgM) developmental pathways through B1 and B2 B cells from fetal liver (FL) and bone marrow (BM). B1 cells develop FL where they go through pro-B cell, pre-B cell, immature B cell, and naïve B cells expressing IgM and CD5 which differentiates B1a and B1b cells, both capable of secreting natural IgM (A). B2 cells develop from BM’s common lymphoid progenitor to become immature B cells that migrate to splenic B cells secreting IgM. Expression of IgD differentiates marginal zones vs. follicular B cells (B). Follicular B cells upon antigen stimulation can either undergo germinal center maturation creating long-lived plasma cells, memory B cells, class switch, or remain unswitched short-lived plasma cells (C). Created with BioRender.com.

Figure 2
Figure 2

The structure of membrane bound and secreted immunoglobulin M (sIgM). (A) A monomer structure of immunoglobulin M (IgM) contains Fab fragments, Fc fragment, and transmembrane signaling tail that attaches to Fc receptors on the surface of B cells. A monomer is made up of two heavy chains and two light chains. (B) A pentamer structure is the most naturally occurring form with five monomers held together by a J-chain. Secretary component regulates surface availability and secretion of the pentamer. Created with BioRender.com.

Figure 3
Figure 3

Immunoglobulin M (IgM) is central at steady stage and against infections and non-communicable diseases. Secretory IgM is important at mucosal surfaces in maintenance of healthy microbiota together with secreted IgA. Secretory IgM together with IgM B cell receptor are important in initiation protective immunity against various respiratory pathogens including species of fungi, viruses, and bacteria. Secreted IgM is essential in parasitic infections including those causing malaria and sleeping sickness. Secreted IgM play an important part in cancers diagnosis and auto-immunity diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Secreted IgM has high affinity for C1q, a complement component that allows degradation of antibody coated pathogens and apoptotic debris. Created with BioRender.com.

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