Germinal center entry not selection of B cells is controlled by peptide-MHCII complex density.
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B cells expressing high affinity antigen receptors are advantaged in germinal centers (GC), perhaps by increased acquisition of antigen for presentation to follicular helper T cells and improved T-cell help. In this model for affinity-dependent selection, the density of peptide/MHCII (pMHCII) complexes on GC B cells is the primary determinant of selection. Here we show in chimeric mice populated by B cells differing only in their capacity to express MHCII (MHCII+/+ and MHCII+/-) that GC selection is insensitive to halving pMHCII density. Alone, both B cell types generate identical humoral responses; in competition, MHCII+/+ B cells are preferentially recruited to early GCs but this advantage does not persist once GCs are established. During GC responses, competing MHCII+/+ and MHCII+/- GC B cells comparably accumulate mutations and have indistinguishable rates of affinity maturation. We conclude that B-cell selection by pMHCII density is stringent in the establishment of GCs, but relaxed during GC responses.
Mice, Inbred C57BL
Genes, MHC Class II
Published Version (Please cite this version)10.1038/s41467-018-03382-x
Publication InfoYeh, Chen-Hao; Nojima, Takuya; Kuraoka, Masayuki; & Kelsoe, Garnett (2018). Germinal center entry not selection of B cells is controlled by peptide-MHCII complex density. Nature communications, 9(1). pp. 928. 10.1038/s41467-018-03382-x. Retrieved from https://hdl.handle.net/10161/19410.
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James B. Duke Distinguished Professor of Immunology
1. Lymphocyte development and antigen-driven diversification of immunoglobulin and T cell antigen receptor genes. 2. The germinal center reaction and mechanisms for clonal selection and self - tolerance. The origins of autoimmunity. 3. Interaction of innate- and adaptive immunity and the role of inflammation in lymphoid organogenesis. 4. The role of secondary V(D)J gene rearrangment in lymphocyte development and malignancies. 5. Mathematical modeling of immune responses,
Research Associate, Senior
Dr. Garnett Kelsoe's Laboratory
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