Correction of the molecular defect in B lymphocytes from X-linked agammaglobulinemia by cell fusion.
The X chromosome-linked antibody deficiency disease, X-linked agammaglobulinemia (XLA), results from failure of B lymphoid development. In the minor form of XLA, B lymphoid development terminates at the stage of immature B lymphocytes that produce truncated Ig heavy (H) chains composed of D-J-C(mu/delta), resulting from failure of VH gene rearrangement. Fusion of B cells from a patient with the minor form of XLA with mouse myeloma results in complementation of this defect; hybrid cells produce full-length H chains composed of VH-D-JH-C. The VH gene is of human origin. Complementation occurs independent of retention or loss of the human X (XLA) chromosome in the hybrid cells. These results indicate that the D-JH-C structure of the XLA B cells is fully functional for the subsequent rearrangement of a VH gene element, and that failure of immunoglobulin expression is susceptible to correction.
D000361:Agammaglobulinemia / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002459:Cell Fusion; D002460:Cell Line; D003001:Cloning, Molecular; D015321:Gene Rearrangement; D008040:Genetic Linkage; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D010954:Plasmacytoma / Q000235:genetics / Q000473:pathology; D014960:X Chromosome
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region