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Positive selection of IgG(+) over IgM(+) B cells in the germinal center reaction


Positive selection of high-affinity B cells within germinal centers (GCs) drives affinity maturation of antibody responses. Here, we examined the mechanism underlying the parallel transition from immunoglobulin M (IgM) to IgG. Early GCs contained mostly unswitched IgM(+) B cells; IgG(+) B cells subsequently increased in frequency, dominating GC responses 14-21 days after antigen challenge. Somatic hypermutation and generation of high-affinity clones occurred with equal efficiency among IgM(+) and IgG(+) GC B cells, and inactivation of Ig class-switch recombination did not prevent depletion of IgM(+) GC B cells. Instead, high-affinity IgG(+) GC B cells outcompeted high-affinity IgM(+) GC B cells via a selective advantage associated with IgG antigen receptor structure but independent of the extended cytoplasmic tail. Thus, two parallel forms of GC B-cell-positive selection, based on antigen receptor variable and constant regions, respectively, operate in tandem to ensure high-affinity IgG antibodies predominate in mature serum antibody responses.

Type Journal
Authors Sundling, C.; Lau, A. W. Y.; Bourne, K.; Young, C.; Laurianto, C.; Hermes, J. R.; Menzies, R. J.; Butt, D.; Krautler, N. J.; Zahra, D.; Suan, D.; Brink, R.
Published Date 2021-05-31
Published Volume 54
Published Issue 5
Published Pages 988-1001
Status Published in-print
DOI 10.1016/j.immuni.2021.03.013
URL link to publisher's version