Early determination of B cell fate

Antibody responses by B cells become more specific over time in a process known as 'affinity maturation', but the role of antibody affinity for antigens in controlling B lymphocyte selection remains unclear. In 20 May Nature Immunology, Tien-An Yang Shih and colleagues from Rockefeller University, New York, show that strict selection for high-affinity B cell clones is imposed at an early stage of the T cell-dependent immune response in vivo (Nat Immunol 2002, DOI: 10.1038/ni803).Shih et al. comp

By | May 22, 2002

Antibody responses by B cells become more specific over time in a process known as 'affinity maturation', but the role of antibody affinity for antigens in controlling B lymphocyte selection remains unclear. In 20 May Nature Immunology, Tien-An Yang Shih and colleagues from Rockefeller University, New York, show that strict selection for high-affinity B cell clones is imposed at an early stage of the T cell-dependent immune response in vivo (Nat Immunol 2002, DOI: 10.1038/ni803).

Shih et al. compared T cell-dependent immune responses to the hapten 4-hydroxyl-3-nitrophenyl acetyl (NP) in mice that carry targeted VHB1-8 antibody genes with high or low antigen-binding affinity. They observed that high and low-affinity B cells were equally able to respond to antigen in the absence of competition. But when limiting numbers of high- and low-affinity B cells were mixed in wild type recipient mice, only the high-affinity B cells accumulated in germinal centers (GC).

"The B cells recruited to the GC appeared to undergo a fixed mutation program, regardless of initial B cell receptor affinity," wrote the authors.

"We conclude that antibody affinity does not regulate the rate of somatic hypermutation and that accumulation of mutations in antibody genes in GC B cells is the result of a preset mutation program followed by selection," say the authors.

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