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

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.

Interleukin (IL)-21 Promotes the Differentiation of IgA-Producing Plasma Cells in Porcine Peyer's Patches via the JAK-STAT Signaling Pathway

“…IL-21, a type 1 cytokine mainly produced by CD4 + T cells and natural killer T cells (NKT), shows pleiotropic effects on a variety of immune cells. IL-21 binds to the receptor IL-21R dominantly expressed on B cells and enhances B cell proliferation, maturation, plasma cell and memory B cell differentiation, and immunoglobulin class switching in mouse models and human studies (27)(28)(29). A previous study showed that IL-21 drove the proliferation and differentiation of porcine spleen B cells into antibody-secreting cells (30).…”

New preclinical models for angioimmunoblastic T-cell lymphoma: filling the GAP

“…Tfh cells also secrete IL-21 and IL-4, two cytokines contributing to B-cell proliferation in the germinal center 25 . Interestingly, CD10 a surface molecule expressed by both neoplastic and normal Tfh, delineates a subset of IL-4 producing Tfh cells 26 .…”

Immunology & Cell Biology’s Top 10 original research articles 2019–2020

“… Robinson et al 1 . BAFF, IL‐4 and IL‐21 separably program germinal centre‐like phenotype acquisition, BCL6 expression, proliferation and survival of CD40L‐activated B cells in vitro Jeong et al 2 .…”

“…While CD40 has arisen as a crucial activator of B cells in T‐cell‐dependent humoral immune responses, studies by Jeong et al 2 . and Robinson et al 1 . explore the other signals involved in germinal center formation and phenotypic acquisition.…”