The germinal center response.
The germinal center reaction is the foundation of T-cell-dependent humoral responses. Antigen-specific B cells recruited into germinal centers undergo a complex cellular program that allows for extensive expansion, isotype switching, somatic hypermutation, and differentiation into antibody-forming cells and memory cells. Importantly, the germinal center environment filters the repertoire of differentiating B cells such that high affinity variants are preferentially selected while low affinity or self-reactive clones are eliminated by apoptosis. The present article reviews the many processes that govern germinal center B-cell differentiation, as well as the cellular and molecular elements necessary to initiate and sustain a germinal center response. The major histologic features of the germinal center are also discussed, as well as the current dominant models of the germinal center reaction in humans and mice. Finally, a new model of murine B-cell differentiation is described on the basis of a multiparameter flow cytometric kinetic analysis of germinal center B cells.
Department of Pathology, Interdisciplinary Immunology Program, and Medical Scientist Training Program, University of Iowa College of Medicine, Iowa City, IA 52242, USA.
Kristy L
KL
Wolniak
Stephen M
SM
Shinall
Thomas J
TJ
Waldschmidt
D000818:Animals; D000917:Antibody Formation / Q000276:immunology* / Q000502:physiology; D000941:Antigens / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology / Q000502:physiology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D018858:Germinal Center / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D006241:Haptens / Q000276:immunology; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology; D018448:Models, Immunological; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000502:physiology
D000941:Antigens; D015703:Antigens, CD; D000954:Antigens, Surface; D006241:Haptens; D011947:Receptors, Antigen, B-Cell