ANTIGEN RECEPTOR ENGAGEMENT TURNS OFF THE V(D)J RECOMBINATION MACHINERY IN HUMAN TONSIL B-CELLS

The germinal center (GC) is an anatomic compartment found in periphera l lymphoid organs, wherein B cells undergo clonal expansion, somatic m utation, switch recombination, and reactivate immunoglobulin gene V(D) J recombination. As a result of somatic mutation, some GC B cells deve lop higher affinity antibodies, whereas others suffer mutations that d ecrease affinity, and still others may become self-reactive It has bee n proposed that secondary V(D)J rearrangements in GCs might rescue B c ells whose receptors are damaged by somatic mutations. Here we present evidence that mature human tonsil B cells coexpress conventional ligh t chains and recombination associated genes, and that they extinguish recombination activating gene and terminal deoxynucleotidyl transferas e expression when their receptors are cross-linked. Thus, the response of the recombinase to receptor engagement in peripheral B cells is th e opposite of the response in developing B cells to the same stimulus. These observations suggest that receptor revision is a mechanism for receptor diversification that is turned off when antigen receptors are cross-linked by the cognate antigen.