Natural IgM prevents autoimmunity by enforcing B cell central tolerance induction

Trang T T Nguyen, Rebecca A. Elsner, Nicole Baumgarth

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

It is unclear why selective deficiency in secreted (s)IgM causes Ab-mediated autoimmunity. We demonstrate that sIgM is required for normal B cell development and selection. The CD5+ B cells that were previously shown to accumulate in body cavities of sIgM-/-mice are not B-1a cells, but CD19int, CD43-, short-lived, BCR signaling-unresponsive anergic B-2 cells. Body cavity B-1 cells were >10-fold reduced, including VH11+ and phosphotidylcholine-specific B-1a cells, whereas splenic B-1 cells were unaffected and marginal zone B cells increased. Follicular B cells had higher turnover rates, survived poorly after adoptive transfer, and were unresponsiveness to BCR stimulation in vitro. sIgM bound to B cell precursors and provided a positive signal to overcome a block at the pro/pre-B stage and during IgVH repertoire selection. Polyclonal IgM rescued B cell development and returned autoantibody levels to near normal. Thus, natural IgM deficiency causes primary autoimmune disease by altering B cell development, selection, and central tolerance induction.

Original languageEnglish (US)
Pages (from-to)1489-1502
Number of pages14
JournalJournal of Immunology
Volume194
Issue number4
DOIs
StatePublished - Feb 15 2015

ASJC Scopus subject areas

  • Immunology

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