Using H-2-congenic NZB, NZW and NZB/W F1 mice, we studied the effect of H-2 haplotype on the frequencies of CD 5
+ B cells in the spleen and peritoneal cavity. We found that in the spleen of all the congenic strains with H-2
Z/H-2
Z haplotype, there were much higher frequencies of CD 5
+ B cells than in the spleen of those with H-2
d/H-2
d or H-2
d/H-2
z haplotypes. These cells eventually proliferated in an oligoclonal or even monoclonal fashion, and B cell-chronic lymphocytic leukemia (B-CLL) developed in some cases. These findings suggest that a locus or cluster of loci closely linked to the H-2
z complex of the N ZW strain may control the high frequency of CD 5
+B cells in the spleen. By contrast, the CD 5
+B cell frequency in the peritoneal cavity did not differ among the H2-congenic strains. Therefore, the frequencies of these cells in the peritoneal cavity and in the spleen appear to be under separate control. Flow cytometry and Southern blot analyses using an immunoglobulin gene J
H proberevealed that in the H-2
Z/H-2
Z homozygotes, there was propagation of distinct clonal populations between the spleen and the peritoneal cavity. All our findings imply that certain different but related haplotypes of a major histocompatibility complex may predispose either to B-CLL or to autoimmune disease, in close relatives.
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