The development and survival but not function of follicular B cells is dependent on IL-7Rα Tyr449 signaling. (CCR1P.242)

Abstract

Abstract IL-7 is a critical cytokine for lymphocyte development but its role in B cells is less well characterized. Using a knock-in mouse with a Tyr to Phe mutation at position 449 (IL-7Rα449F/449F mice) within the cytoplasmic domain of IL-7Rα, we evaluated the role of this YxxM motif in spleen B cells. IL-7Rα449F/449F mice had reduced numbers and increased death of follicular B cells compared to WT, but had significantly more follicular cells than IL-7Rα-/-. The death of IL-7Rα449F/449F follicular cells was not due to a failure to respond to BAFF or lower levels of BAFF. Marginal zone B cells were unaffected in IL-7Rα449F/449F mice. A role for TSLP was ruled out, as TSLPR-/- mice had an identical B cell phenotype to wild-type mice. Bone marrow chimeras and the absence of IL-7Rα on B cells suggested that IL-7 did not directly regulate mature B cells, but that an IL-7-responsive cell was influencing B cells. IL-7 was also critical at the checkpoint between the T1 and T2 stages in the spleen. We tested the functional responses of IL-7Rα449F/449F mice and found no difference in antibody responses to T-dependent or T-independent antigens, or to Influenza/A. IL-7 was important for generation of antibody responses to the intestinal worm H. polygyrus and for naive levels of IgA. Our data shows that IL-7 regulates follicular B cell numbers and survival in a cell-extrinsic manner, via a bone-marrow derived cell, but is not critical for antibody production outside the gut.