PREFERENTIAL UTILIZATION OF THE IMMATURE J(H) SEGMENT AND ABSENCE OF SOMATIC MUTATION IN THE CDR3 JUNCTION OF THE IG H-CHAIN GENE IN 3 X-LINKED SEVERE COMBINED IMMUNODEFICIENCY PATIENTS

Human severe combined immunodeficiency (SCID) includes an X-linked SCI D (XSCID) characterized by a complete absence of mature T cells, hypog ammaglobulinemia and a normal or elevated number of B cells. XSCID res ults from mutation in the IL-2 receptor (IL-2R) gamma chain gene, whic h is thought to be involved in not only IL-2R but also IL-4R and IL-7R mediated signals. To investigate the VDJ recombination and Ig reperto ire development in the absence of the IL-2R gamma chain, we intended t o study the CDR3 junction in peripheral blood B cells of three XSCID p atients. A total of 101 different CDR3 junctions were cloned following polymerase chain reaction amplification of polyclonal peripheral bloo d lymphocyte DNA. Sequence analysis of CDR3 junctions revealed that th e primary antibody repertoire of the Ig H chain gene was assembled in a normal fashion. Among the JH segments, overexpression of J(H)3 segme nts was significant in XSCID patients compared with age-matched contro ls. D segment usage in XSCID was very similar to that in age-matched c ontrols. All of the XSCID J(H) regions except for two clones were equa l to germline J(H) genes, showing little or no evidence of somatic mut ation. The results indicate that the immature J(H) Segment is preferen tially utilized and somatic mutation is absent in the CDR3 junction of the Ig H chain gene of XSCID patients.