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Immunity ; 54(5): 988-1001.e5, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33857421

RESUMO

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.


Assuntos
Linfócitos B/imunologia , Centro Germinativo/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Animais , Formação de Anticorpos/imunologia , Antígenos/imunologia , Feminino , Switching de Imunoglobulina/imunologia , Região Variável de Imunoglobulina/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Ovinos/imunologia , Hipermutação Somática de Imunoglobulina/imunologia
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