The Journal of Immunology, Vol 141, Issue 5 1738-1744, Copyright © 1988 by American Association of Immunologists

ARTICLES

Gene mutations and alternate RNA splicing result in truncated Ig L chains in human gamma H chain disease

M Cogne, A Bakhshi, SJ Korsmeyer and P Guglielmi
Institut National de la Sante de la Recherche Medicale U108, Paris, France.

The lack of covalently associated L chains features H chain disease proteins produced in some human B cell lymphoproliferative disorders. We cloned and characterized the single rearranged kappa L chain gene from the leukemic lymphocytes of a patient (RIV) affected with gamma 1 H chain disease, to determine the molecular basis for absent L chain. This kappa allele had undergone an effective V-J rearrangement. Extensive somatic mutation focused about the V-J region created a sequence that was only 75% homologous to its germ-line counterpart. Altered acceptor (V kappa) and donor (J kappa) splice sites resulted in an aberrant splice between the leader and C kappa exons and a truncated 850-bp kappa mRNA. RIV leukemic cells as well as myeloma cells transfected with the RIV kappa gene synthesized a truncated protein. Simultaneous defects in H and L chains genes may reflect a hypermutational mechanism for Ig genes in B cells.

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