IMMUNOGLOBULIN V-H GENE SEQUENCE-ANALYSIS OF SPONTANEOUS MURINE IMMUNOGLOBULINSECRETING B-CELL TUMORS WITH CLINICAL-FEATURES OF HUMAN-DISEASE

The 5T series of multiple myelomas (MM) and Waldenstrsom's macroglobul inaemia-like lymphomas (WM), which developed spontaneously in ageing m ice of the C57BL/KaLwRij strain, shows clinical and biological feature s that closely resemble their corresponding human diseases. In order t o compare the patterns of somatic mutation in V-H genes of mouse tumou rs with those of human counterparts, we have determined and analysed s equences of immunoglobulin V-H genes in five cases of murine MM, two o f WM and one of biclonal benign monoclonal gammopathy (BMG), Four of f ive MM and 2/2 WM cases used V-H genes of the large J558 family; one M M used a gene of the VGAM3.8 family, and both clones of the BMG used g enes of the 36-60 family. N-region insertions were observed in all cas es, but D-segment genes were only identified in 6/9 cases, which were all from the D-SP family and translated in reading frame 3. Compared w ith human MM. in which the V-H genes have been found to be consistentl y hypermutated (mean% +/- SD = 8.8 +/- 3.2), the degree of somatic mut ation in the murine tumours was significantly loner (mean% +/- SD = 2. 9 +/- 2.3). There was no significant evidence of clustering of replace ment mutations in complementarity determining regions (CDR), a feature considered to be characteristic of antigen-selected sequences. Howeve r, one clone of the biclonal BMG case showed intraclonal variation, a feature described in some cases of human BMG. These results indicate t hat murine V-H genes in mature tumours differ from human counterparts in the level and distribution of somatic mutations, but support the co ncept that BMG may be distinct from MM.