TY - JOUR
T1 - Natural IgM prevents autoimmunity by enforcing B cell central tolerance induction
AU - Nguyen, Trang T T
AU - Elsner, Rebecca A.
AU - Baumgarth, Nicole
PY - 2015/2/15
Y1 - 2015/2/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1401880
DO - 10.4049/jimmunol.1401880
M3 - Article
C2 - 25595791
AN - SCOPUS:84922572798
VL - 194
SP - 1489
EP - 1502
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 4
ER -