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

Trang T T Nguyen, Nicole Baumgarth

Research output: Contribution to journalReview articlepeer-review

27 Scopus citations


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
Issue number2
StatePublished - 2016


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

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)


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