The T cell-dependent processes of class switch recombination (CSR) and immune maturation are believed to be driven by affinity-dependent clonal selection. However, analysis of the anti-hapten 2-phenyloxazolone response reveals that (i) thymus-dependent IgM are as heterogene-ous as natural and thymus-independent antibodies, (ii) many IgM exhibit similar or greater affinities than the classic Ox1 clonotype that (iii) dominates only after CSR, (iv) CSR selects B cell clones with shorter and more uniform CDR-H3 lengths and (v) primary IgM encoded by VH1 family genes were almost completely eliminated from the repertoire by CSR. Thus, contrary to the current paradigm, CSR appears to be clonally regulated more on the basis of BCR-specific, e.g. CDR-H3 idiotope-related, T cell action than affinity-dependent clonal selection.
- Copyright © 2011 by The American Association of Immunologists, Inc.