VH GENE USAGE IN HUMANS - BIASED USAGE OF THE VH6 GENE IN IMMATURE B-LYMPHOID CELLS

Preferential usage of J(H)-proximal V(H) genes has been demonstrated in immature murine B cell repertoires. To determine whether this phenomenon is also evident in human repertoires, we studied utilization of V(H)6, the most J(H)-proximal human V(H) gene. Examination of V(H) gene usage in a panel of precursor B cell acute lymphoblastic leukemia samples indicated that 15% of the IgH rearrangements utilized V(H)6. V(H)6 is a single-member family in a total repertoire of 100-200 V(H) genes; thus, if usage were purely random, one would expect V(H)6 rearrangement frequency to be < 1%. Analysis of V(H) gene usage in normal lymphoid tissues also revealed biased usage of V(H)6. V(H)6 was preferentially utilized in 16- to 24-week-old fetal liver as compared to adult peripheral blood mononuclear cells or spleen. Possible implications of the conservation of preferential usage of J(H)-proximal genes in both immature murine and human repertoires are discussed.