Natural IgM and the development of B cell-mediated autoimmune diseases

Trang T T Nguyen, Nicole Baumgarth

Research output: Contribution to journalReview article

17 Citations (Scopus)

Abstract

Most serum immunoglobulin M (IgM) is “natural IgM,” which is produced apparently spontaneously by a distinct subset of B cells requiring no exogenous antigenic or microbial stimuli. Natural IgM is an evolutionarily conserved molecule and reacts with a variety of epitopes expressed on both self-and non-self antigens. It has long been understood that secreted (s) IgM contributes to the removal of altered self-antigens, such as apoptotic and dying cells. As we outline in this review, it is thought that this sIgM housekeeping function removes potential triggers of autoresponse induction. However, we recently demonstrated an unexpected and distinct role for sIgM in the control of autoreactive B cells: the regulation of bone marrow B cell development. The absence of sIgM blocked pro-to pre-B-cell transition and greatly altered the BCR repertoire of the developing B cells and the peripheral B-cell pools in genetically engineered mice. This finding strongly suggests that IgM is critical for B-cell central tolerance induction. Given that treatment of sIgM-deficient mice with polyclonal IgM corrected these developmental defects, therapeutic application of IgM could be of clinical relevance in the treatment of some B-cell-mediated autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)163-177
Number of pages15
JournalCritical Reviews in Immunology
Volume36
Issue number2
DOIs
StatePublished - 2016

Fingerprint

Autoimmune Diseases
Immunoglobulin M
B-Lymphocytes
Central Tolerance
B-Lymphocyte Subsets
Housekeeping
B-Lymphoid Precursor Cells
Autoantigens
Bone Marrow Cells
Epitopes
Therapeutics
Antigens
Serum

Keywords

  • B-1 cells
  • B-cell development
  • IgM-deficiency
  • Tolerance induction

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Natural IgM and the development of B cell-mediated autoimmune diseases. / Nguyen, Trang T T; Baumgarth, Nicole.

In: Critical Reviews in Immunology, Vol. 36, No. 2, 2016, p. 163-177.

Research output: Contribution to journalReview article

@article{207f7e2f7d16474385b2b8288e1d7bd6,
title = "Natural IgM and the development of B cell-mediated autoimmune diseases",
abstract = "Most serum immunoglobulin M (IgM) is “natural IgM,” which is produced apparently spontaneously by a distinct subset of B cells requiring no exogenous antigenic or microbial stimuli. Natural IgM is an evolutionarily conserved molecule and reacts with a variety of epitopes expressed on both self-and non-self antigens. It has long been understood that secreted (s) IgM contributes to the removal of altered self-antigens, such as apoptotic and dying cells. As we outline in this review, it is thought that this sIgM housekeeping function removes potential triggers of autoresponse induction. However, we recently demonstrated an unexpected and distinct role for sIgM in the control of autoreactive B cells: the regulation of bone marrow B cell development. The absence of sIgM blocked pro-to pre-B-cell transition and greatly altered the BCR repertoire of the developing B cells and the peripheral B-cell pools in genetically engineered mice. This finding strongly suggests that IgM is critical for B-cell central tolerance induction. Given that treatment of sIgM-deficient mice with polyclonal IgM corrected these developmental defects, therapeutic application of IgM could be of clinical relevance in the treatment of some B-cell-mediated autoimmune diseases.",
keywords = "B-1 cells, B-cell development, IgM-deficiency, Tolerance induction",
author = "Nguyen, {Trang T T} and Nicole Baumgarth",
year = "2016",
doi = "10.1615/CritRevImmunol.2016018175",
language = "English (US)",
volume = "36",
pages = "163--177",
journal = "Critical Reviews in Immunology",
issn = "1040-8401",
publisher = "Begell House Inc.",
number = "2",

}

TY - JOUR

T1 - Natural IgM and the development of B cell-mediated autoimmune diseases

AU - Nguyen, Trang T T

AU - Baumgarth, Nicole

PY - 2016

Y1 - 2016

N2 - Most serum immunoglobulin M (IgM) is “natural IgM,” which is produced apparently spontaneously by a distinct subset of B cells requiring no exogenous antigenic or microbial stimuli. Natural IgM is an evolutionarily conserved molecule and reacts with a variety of epitopes expressed on both self-and non-self antigens. It has long been understood that secreted (s) IgM contributes to the removal of altered self-antigens, such as apoptotic and dying cells. As we outline in this review, it is thought that this sIgM housekeeping function removes potential triggers of autoresponse induction. However, we recently demonstrated an unexpected and distinct role for sIgM in the control of autoreactive B cells: the regulation of bone marrow B cell development. The absence of sIgM blocked pro-to pre-B-cell transition and greatly altered the BCR repertoire of the developing B cells and the peripheral B-cell pools in genetically engineered mice. This finding strongly suggests that IgM is critical for B-cell central tolerance induction. Given that treatment of sIgM-deficient mice with polyclonal IgM corrected these developmental defects, therapeutic application of IgM could be of clinical relevance in the treatment of some B-cell-mediated autoimmune diseases.

AB - Most serum immunoglobulin M (IgM) is “natural IgM,” which is produced apparently spontaneously by a distinct subset of B cells requiring no exogenous antigenic or microbial stimuli. Natural IgM is an evolutionarily conserved molecule and reacts with a variety of epitopes expressed on both self-and non-self antigens. It has long been understood that secreted (s) IgM contributes to the removal of altered self-antigens, such as apoptotic and dying cells. As we outline in this review, it is thought that this sIgM housekeeping function removes potential triggers of autoresponse induction. However, we recently demonstrated an unexpected and distinct role for sIgM in the control of autoreactive B cells: the regulation of bone marrow B cell development. The absence of sIgM blocked pro-to pre-B-cell transition and greatly altered the BCR repertoire of the developing B cells and the peripheral B-cell pools in genetically engineered mice. This finding strongly suggests that IgM is critical for B-cell central tolerance induction. Given that treatment of sIgM-deficient mice with polyclonal IgM corrected these developmental defects, therapeutic application of IgM could be of clinical relevance in the treatment of some B-cell-mediated autoimmune diseases.

KW - B-1 cells

KW - B-cell development

KW - IgM-deficiency

KW - Tolerance induction

UR - http://www.scopus.com/inward/record.url?scp=84994469040&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84994469040&partnerID=8YFLogxK

U2 - 10.1615/CritRevImmunol.2016018175

DO - 10.1615/CritRevImmunol.2016018175

M3 - Review article

C2 - 27910766

AN - SCOPUS:84994469040

VL - 36

SP - 163

EP - 177

JO - Critical Reviews in Immunology

JF - Critical Reviews in Immunology

SN - 1040-8401

IS - 2

ER -