Rearrangement of antigen receptor genes is defective in mice with severe combined immune deficiency.
A process unique to lymphocyte differentiation is the rearrangement of genes encoding antigen-specific receptors on B and T cells. A mouse mutant (C.B-17scid) with severe combined immune deficiency, i.e., that lacks functional B and T cells, shows no evidence of such gene rearrangements. However, rearrangements were detected in Abelson murine leukemia virus-transformed bone marrow cells and in spontaneous thymic lymphomas from C.B-17scid mice. Most of these rearrangements were abnormal: approximately 80% of Igh rearrangements deleted the entire Jh region, and approximately 60% of TCR beta rearrangements deleted the entire J beta 2 region. The deletions appeared to result from faulty D-to-J recombination. No such abnormal rearrangements were detected in transformed tissues from control mice. The scid mutation may adversely affect the recombinase system catalyzing the assembly of antigen receptor genes in developing B and T lymphocytes.
D000011:Abelson murine leukemia virus; D000818:Animals; D002472:Cell Transformation, Viral; D002872:Chromosome Deletion; D004254:DNA Nucleotidyltransferases / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D008223:Lymphoma / Q000235:genetics; D051379:Mice; D009154:Mutation; D011947:Receptors, Antigen, B-Cell / Q000235:genetics*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013950:Thymus Gland; D045567:VDJ Recombinases
D007143:Immunoglobulin Heavy Chains; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases