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Critical Reviews in Immunology, 24(1):39–66 (2004)
The Germinal Center Response
1,2 1 1,2,*
Kristy L. Wolniak, Stephen M. Shinall, Thomas J. Waldschmidt
1Department of Pathology, Interdisciplinary Immunology Program, and 2Medical Scientist Training
Program, University of Iowa College of Medicine, Iowa City, IA 52242
*Author to whom all correspondence should be addressed; email: thomas-waldschmidt@.
Referee: Dr. Paul Rennert, Department of Immunology, Biogen, Inc., 14 Cambridge Center, Cambridge, MA 02142
ABSTRACT: 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 germ
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