Antigen-induced somatic diversification of rabbit IgH genes: Gene conversion and point mutation

During T cell-dependent immune responses in mouse and human, Ig genes diver sify by somatic hypermutation within germinal centers. Rabbits, in addition to using somatic hypermutation to diversify their IgH genes, use a somatic gene conversion-like mechanism, which involves homologous recombination be tween upstream V-H gene segments and the rearranged VDJ genes, Somatic gene conversion and somatic hypermutation occur in young rabbit gut-associated lymphoid tissue and are thought to diversify a primary Ab repertoire that i s otherwise limited by preferential V-H gene segment utilization. Because s omatic gene conversion is rarely found within Ig genes during immune respon ses in mouse and human, we investigated whether gene conversion in rabbit a lso occurs during specific immune responses, in a location other than gut-a ssociated lymphoid tissue. We analyzed clonally related VDJ genes from popl iteal lymph node B cells responding to primary, secondary, and tertiary imm unization with the hapten FITC coupled to a protein carrier. Clonally relat ed VDJ gene sequences were derived from FITC-specific hybridomas, as well a s from Ag-induced germinal centers of the popliteal lymph node. By analyzin g the nature of mutations within these clonally related VDJ gene sequences, we found evidence not only of ongoing somatic hypermutation, but also of o ngoing somatic gene conversion. Thus in rabbit, both somatic gene conversio n and somatic hypermutation occur during the course of an immune response.