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

Patton, D. T., Plumb, A. W., Redpath, S. A., Osborne, L. C., Perona-Wright, G. and Abraham, N. (2014) The development and survival but not function of follicular B cells is dependent on IL-7Rα Tyr449 signaling. PLoS ONE, 9(2), e88771. (doi: 10.1371/journal.pone.0088771) (PMID:24551160) (PMCID:PMC3923819)

Abstract

IL-7 is a critical cytokine for lymphocyte development. Recent work has highlighted critical roles for IL-7 signaling in mature T cell homeostasis and function, but its role in B cells is less well characterized. Using a knock-in mouse possessing a Tyr to Phe mutation at position 449 (IL-7Rα449F/449F mice) within the cytoplasmic SH2-binding motif of IL-7Rα, we evaluated the role of IL-7Rα Y449 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, a critical B cell survival factor. Marginal zone B cells were unaffected by the IL-7Rα449F/449F mutation. Any 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. IL-7Rα−/− mice fail to develop T2 cells, but IL-7Rα449F/449F show a reduction compared to WT but not complete absence of T2 cells. We also tested the functional responses of IL-7Rα449F/449F to antigens and infection 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. Taken together, this suggests 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Perona-Wright, Dr Georgia
• Authors: Patton, D. T., Plumb, A. W., Redpath, S. A., Osborne, L. C., Perona-Wright, G., and Abraham, N.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• ISSN (Online): 1932-6203
• Copyright Holders: Copyright © 2014 Patton et al.
• First Published: First published in PLoS ONE 9(2):e88771
• Publisher Policy: Reproduced under a Creative Commons License