On immunoglobulin heavy chain gene switching: two γ2b genes are rearranged via switch sequences in MPC-11 cells but only one is expressed

Abstract

During B lymphocyte differentiation, switches in the expression of heavy chain immunoglobulin constant region (C_H) genes occur by a novel DNA recombination mechanism. We have investigated the requirements of the C_H gene switch by characterizing two rearranged _γ2b genes from a _γ2b producing mouse myeloma (MPC-11). One of the two _γ2b genes is present in 2-3 copies per cell (_γ2b strong hybridizer) while the other is present in ˜1 copy per cell (_γ2b weak hybridizer). Genomic clones of the _γ2b strongly hybridizing gene indicate that this is an abortive switch event between the S_γ3 and S_γ2b regions. How ever, clones of the _γ2b weakly hybridizing gene suggest a functional rearrangement due to the presence of V_H, J_H and S_μ sequences. The switch-recombination sites of these rearranged _γ2b genes and those of other C_H genes show a high degree of preference for the sequence AGGTTG 5′ of either the S_μ donor site or the appropriate C_H S acceptor site. AGGTTG and its analogs are rare in the S_μ region, are somewhat prevalent in S_α and in the case of S_μ are found 5′ of a tandemly repeated DNA sequence (GAGCT, GGGGT) comprising most of S_μ.