RESTRICTED UTILIZATION OF GERM-LINE VH3 GENES AND SHORT DIVERSE 3RD COMPLEMENTARITY-DETERMINING REGIONS (CDR3) IN HUMAN FETAL LYMPHOCYTE-B IMMUNOGLOBULIN HEAVY-CHAIN REARRANGEMENTS

Twenty-one independent immunoglobulin heavy chain VH3DJH rearrangements were cloned and sequenced from livers of human fetuses at 7, 13 and 18 weeks of gestation. The V(H) elements expressed were not somatically mutated. Eight out of the estimated 30 V(H)3 elements were utilized with a preference for five of them. One of these V(H)3 sequences, designated FL13-28, represented a thus-far unknown V(H)3 gene segment. From the six functional J(H) elements the J(H)3 and J(H)4 segments were utilized preferentially and from the estimated 30 D segments the DQ52 element and the Dxp family were found to rearrange frequently. D elements were utilized both in normal and inverted orientation, as single copies or in D to D fusions. Addition of N nucleotides, removal of nucleotides from the coding sequences and utilization of DIR elements (D genes with irregular recombination signals) further expanded the third complementarity-determining region (CDR3) diversity. One fourth of the fetal CDR3 regions lacked N regions. Due to utilization of DQ52, the relative absence of N regions and extensive exonuclease activity operating on the D elements, the fetal CDR3 regions were significantly shorter than those found in adult B lymphocytes.