IL-21 regulates germinal center B cell differentiation and proliferation through a B cell-intrinsic mechanism
Details
Publication Year 2010-02-15, Volume 207, Issue #2, Page 365-378
Journal Title
JOURNAL OF EXPERIMENTAL MEDICINE
Publication Type
Journal Article
Abstract
Germinal centers (GCs) are sites of B cell proliferation, somatic hypermutation, and selection of variants with improved affinity for antigen. Long-lived memory B cells and plasma cells are also generated in GCs, although how B cell differentiation in GCs is regulated is unclear. IL-21, secreted by T follicular helper cells, is important for adaptive immune responses, although there are conflicting reports on its target cells and mode of action in vivo. We show that the absence of IL-21 signaling profoundly affects the B cell response to protein antigen, reducing splenic and bone marrow plasma cell formation and GC persistence and function, influencing their proliferation, transition into memory B cells, and affinity maturation. Using bone marrow chimeras, we show that these activities are primarily a result of CD3-expressing cells producing IL-21 that acts directly on B cells. Molecularly, IL-21 maintains expression of Bcl-6 in GC B cells. The absence of IL-21 or IL-21 receptor does not abrogate the appearance of T cells in GCs or the appearance of CD4 T cells with a follicular helper phenotype. IL-21 thus controls fate choices of GC B cells directly.
Publisher
ROCKEFELLER UNIV PRESS
Keywords
FOLLICULAR-HELPER-CELLS; PRIMARY IMMUNE-RESPONSE; T-CELLS; PLASMA-CELLS; SYSTEMIC AUTOIMMUNITY; CLONAL SELECTION; IN-VIVO; MEMORY; GENERATION; MICE
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2010-02-15 12:00:00
Last Modified: 0001-01-01 12:00:00
An error has occurred. This application may no longer respond until reloaded. Reload 🗙