BAFF, IL-4 and IL-21 separably program germinal center-like phenotype acquisition, BCL6 expression, proliferation and survival of CD40L-activated B cells in vitro
Robinson MJ, Pitt C, Brodie EJ, Valk AM, O'Donnell K, Nitschke L, Jones S, Tarlinton DM (2019)
Publication Type: Journal article
Publication year: 2019
Journal
DOI: 10.1111/imcb.12283
Abstract
A B cell culture system using BAFF, IL-4 and IL-21 was recently developed that generates B cells with phenotypic and functional characteristics of in vivo-generated germinal center (GC) B cells. Here, we observe discrete influences of each exogenous signal on the expansion and differentiation of a CD40L-activated B cell pool. IL-4 was expressly necessary, but neither BAFF nor IL-21 was required for B cell acquisition of the GC B cell phenotypes of peanut agglutinin binding and loss of CD38 and IgD expression. Both IL-4 and IL-21 enhanced cell cycle entry upon initial activation dose-dependently, and did so additively. Importantly, while both cytokines acted in concert to increase overall BCL6 expression amounts, IL-21 exposure uniquely caused a small proportion of cells to attain a higher level of BCL6 expression, reminiscent of in vivo GC B cells. In contrast, BAFF supported survival of a fraction of memory-like B cells in extended cultures after removal of surrogate T cell-help signals. Thus, by separably programming proliferation, survival and GC phenotype acquisition, IL-4, BAFF and IL-21 drive distinct components of activated B cell fate.
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Australia (AU)How to cite
APA:
Robinson, M.J., Pitt, C., Brodie, E.J., Valk, A.M., O'Donnell, K., Nitschke, L.,... Tarlinton, D.M. (2019). BAFF, IL-4 and IL-21 separably program germinal center-like phenotype acquisition, BCL6 expression, proliferation and survival of CD40L-activated B cells in vitro. Immunology and Cell Biology. https://dx.doi.org/10.1111/imcb.12283
MLA:
Robinson, Marcus J., et al. "BAFF, IL-4 and IL-21 separably program germinal center-like phenotype acquisition, BCL6 expression, proliferation and survival of CD40L-activated B cells in vitro." Immunology and Cell Biology (2019).
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