The scid defect affects the final step of the immunoglobulin VDJ recombinase mechanism

• Published in: Cell Vol. 54; no. 4; pp. 453 - 460
• Main Authors: Malynn, Barbara A., Blackwell, T.Keith, Fulop, Gabrielle M., Rathbun, Gary A., Furley, Andrew J.W., Ferrier, Pierre, Heinke, L.Bruce, Phillips, Robert A., Yancopoulos, George D., Alt, Frederick W.
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 12.08.1988; Cell Press
• Subjects: Abelson murine leukemia virus; Animals; Base Sequence; Biological and medical sciences; Cell Transformation, Viral; DNA Nucleotidyltransferases - genetics; DNA Nucleotidyltransferases - metabolism; Fundamental and applied biological sciences. Psychology; Genic rearrangement. Recombination. Transposable element; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Variable Region - genetics; Immunologic Deficiency Syndromes - genetics; Mice; Mice, Mutant Strains; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Recombination, Genetic; VDJ Recombinases; Oncovirinae; Immunoglobulins; Nucleotide sequence; Rodentia; Retroviridae; B-Lymphocyte; Recombinant DNA; Precursor; Virus; Vertebrata; Mammalia; Mouse; Type C oncovirus; Molecular rearrangement; Murine leukemia virus; Mutation
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/0092-8674(88)90066-9

Abelson murine leukemia virus-transformed precursor B lymphocytes from sci (severe combined immunodeficient) mice, like A-MuLV transformants from normal mice, actively rearrange segments of their lg heavy chain variable region gene locus during growth in culture. Targeting of recombination to appropriate segments appears normal in these lines as evidenced by initial rearrangement of sequences from within the D and J H locus to from aberrant “DJ H” rearrangements and secondary rearrangement of sequences from within the V H locus to the aberrant “DJ H” intermediates. A detailed analysis of the joints in these rearrangements indicates that the VDJ recombinase in scid pre-B cells can correctly recognize heptamer-nonamer signal sequences and perform precise endonucleolytic scissions at these sequences. We propose that the scid defect involves the inability of scid precursor lymphocytes to join correctly the cleaved ends of the coding strands of variable region gene segments.