Sequential expression of germ line genes in development of immunoglobulin class diversity

Abstract

Differentiation of B cells occurs in two discontinuous stages. Primary differentiation of stem cells to B lymphocytes in birds occurs exclusively in the lymphoepithelial bursa of Fabricius; the fetal liver may serve this function in mammals. In chickens both the size of the B lymphocyte pool and the generation of precursors for cells secreting different immunoglobulin classes is controlled by the bursa. The latter process involves the sequential expression of genes coding for heavy chain constant regions in the order μ, γ, α. The second stage of B cell differentiation is antigen driven, and involves proliferation and maturation of B lymphocytes to plasma cells. Ontogenetic development of different classes of B lymphocytes in mammals is orderly, independent of exogenous antigens, and occurs in the sequence μ, γ, α. A developmental switch in expression, of G(H) genes, beginning with μ, has been experimentally verified. This hypothesises that generation of class diversity of B lymphocytes occurs during the antigen independent first stage of differentiation, and that the genetic switch in C(H) gene expression follows the sequence μ→γ→α, but evidence of these points remains inconclusive.