Somatic mutation of immunoglobulin lambda chains: a segment of the major intron hypermutates as much as the complementarity-determining regions

Abstract

The rate and nature of hypermutation of immunoglobulin genes are of prime importance in the affinity maturation of antibodies. Although a considerable body of information has been gathered for κ light chains, there is much less data for λ chains. We have derived a large data base of somatic mutants of mouse λ 1 light chains from Peyer's patches germinal center B cells. The endogenous λ 1 genes mutate at a rate comparable to that previously found for a κ transgene (V κ ox1). There are intrinsic hot spots of mutation common to both in-frame and out-of-frame rearrangements; these hot spots cluster in hypermutating domains. In contrast to the pattern seen for V κ Ox1, the hot spot clusters are found not only in complementarity-determining region (CDR)1 but also in CDR2 and CDR3; mutations also cluster in the joining/constant region intron. The differences between the pattern of mutations in V κ Ox1 and λ 1 light chains are discussed.