Interspersion of the VHQ52 and VH7183 gene families in the NFS/N mouse.
Deletion mapping analysis has shown that members of the VH7183 and VHQ52 gene families are interspersed in the NFS/N mouse. To obtain direct evidence that members of these gene families are physically linked, an NFS/N liver library was constructed and genomic clones were analyzed for hybridization to both VHQ52 and VH7183 gene probes. Four clones were identified which contained both VHQ52 and VH7183 hybridizable restriction fragments. Two clones containing rearranged VHQ52 genes were also found to hybridize with the VH7183 gene probe. Sequence analysis of three of the VH7183-containing restriction fragments indicate that all are pseudogenes which contain interruptions at either the 5' and/or 3' ends of the VH coding region. Given the D-proximal location of at least a portion of the VHQ52 gene family relative to VH7183 in NFS/N mice, and the known correlation between D proximity and the frequency of VH gene utilization, 22 NFS/N-derived pre-B cell lines were analyzed for VHQ52 gene utilization. More than 40% of the identified H chain (VHDJH) rearrangements in this survey used members of this gene family. Furthermore, analysis of poly(A)+ RNA from NFS/N fetal liver and adult spleen also indicates preferential utilization of VHQ52 family in fetal liver. Kinetic studies show, however, that there are no changes in relative utilization throughout fetal ontogeny. The implications of these findings for the expression and randomization of the VH repertoire are discussed.
Kleinfield
R W
RW
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111.
Weigert
M G
MG
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000032:analysis; D001483:Base Sequence; D002461:Cell Line, Transformed; D003001:Cloning, Molecular; D005314:Embryonic and Fetal Development; D015322:Gene Rearrangement, B-Lymphocyte; D008040:Genetic Linkage; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000302:isolation & purification; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000302:isolation & purification; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D005810:Multigene Family; D013154:Spleen / Q000378:metabolism; D013234:Stem Cells / Q000032:analysis
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region