SOMATIC MUTATION OF IMMUNOGLOBULIN-LAMBDA CHAINS - A SEGMENT OF THE MAJOR INTRON HYPERMUTATES AS MUCH AS THE COMPLEMENTARITY-DETERMINING REGIONS

The rate and nature of hypermutation of immunoglobulin genes are of pr ime importance in the affinity maturation of antibodies. Although a co nsiderable body of information has been gathered for kappa light chain s, there is much less data for lambda chains. We have derived a large data base of somatic mutants of mouse lambda 1 light chains from Peyer 's patches germinal center B cells. The endogenous lambda 1 genes muta te at a rate comparable to that previously found for a kappa transgene (V kappa ox1). There are intrinsic hot spots of mutation common to bo th in-frame and out-of frame rearrangements; these hot spots cluster i n hypermutating domains. In contrast to the pattern seen for V kappa O x1, the hot spot clusters are found not only in complementarity-determ ining region (CDR)1 but also in CDR2 and CDR3; mutations also cluster in the joining/constant region intron. The differences between the pat tern of mutations in V kappa Ox1 and lambda 1 light chains ace discuss ed.