Avian B-Cell Development: Generation of an Immunoglobulin Repertoire by Gene Conversion

Abstract

The vertebrate B-cell repertoire is capable of generating up to 10(9) different antibody molecules using relatively few germline immunoglobulin (Ig) gene segments. To generate diversity, humans and mice depend on combinatorial and junctional variations that occur during the gene rearrangement events that produce complete heavy and light chain Ig genes. This gene rearrangement process goes on continuously in the bone marrow, where each developing B cell assembles a unique heavy and light chain Ig gene from families of functional V, D, and J gene segments. In contrast, chickens have only single functional V and J segments for the heavy and light chain loci, and chicken Ig gene rearrangement occurs only during a brief period of embryonic development. A specialized organ involved in avian B-cell development, the bursa of Fabricius, provides the microenvironment necessary for the amplification of B cells that have undergone productive Ig gene rearrangements. Within the bursa, B cells also acquire somatic diversity within the rearranged V gene segments of the heavy and light chain Ig loci. Somatic diversification of chicken V gene segments occurs by intrachromosomal gene conversion, a DNA recombination process which involves unidirectional transfer of nucleotide sequence blocks from families of V region pseudogenes into the functional rearranged VH and VL genes.