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.
|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.|
|Publisher Name||INFECTION AND IMMUNITY|
|URL link to publisher's version||https://www.ncbi.nlm.nih.gov/pubmed/33857421|