Mouse V_k gene classification by nucleic acid sequence similarity

Analyses of immunoglobulin (Ig) variable (V) region gene usage in the immune response, estimates of V gene germline complexity, and other nucleic acid hybridization-based studies depend on the extent to which such genes are related (i. e., sequence similarity) and their organization in gene families. While mouse Igh heavy chain V region (V_H) gene families are relatively well-established, a corresponding systematic classification of Igk light chain V region (V_k) genes has not been reported. The present analysis, in the course of which we reviewed the known extent of the V_k germline gene repertoire and V_k gene usage in a variety of responses to foreign and self antigens, provides a classification of mouse V_k genes in gene families composed of members with >80% overall nucleic acid sequence similarity. This classification differed in several aspects from that of V_H genes: only some V_k gene families were as clearly separated (by >25% sequence dissimilarity) as typical V_H gene families; most V_k gene families were closely related and, in several instances, members from different families were very similar (>80%) over large sequence portions; frequently, classification by nucleic acid sequence similarity diverged from existing classifications based on amino-terminal protein sequence similarity. Our data have implications for V_k gene analyses by nucleic acid hybridization and describe potentially important differences in sequence organization between V_H and V_k genes.