Natural IgM Prevents Autoimmunity by Enforcing B Cell Central Tolerance Induction

作者：Nguyen Trang T T; Elsner Rebecca A; Baumgarth Nicole^*

来源：The Journal of Immunology, 2015, 194(4): 1489-1502.

DOI：10.4049/jimmunol.1401880

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 CD19(int), 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.

• 出版日期2015-2-15