Limited repertoire of utilized VH gene segments in a VHa3-allotype-suppressed rabbit.
Between 70 and 90% of serum Ig molecules of normal laboratory rabbits bear one of the serologically defined VHa allotypic specificities, a1, a2, or a3, and are termed VHa+ (a-positive) molecules; the remaining 10-30% of Ig molecules that do not have VHa allotypic specificities are designated VHa- (a-negative). The repertoire of utilized VHa(+)-encoding gene segments has been examined extensively, but only limited studies of the repertoire of utilized VHa(-)-encoding gene segments in normal rabbits have been done. To examine the repertoire of utilized VHa- gene segments, we analyzed VH-encoding cDNA clones from mRNA of a VHa-allotype-suppressed rabbit whose serum Ig was primarily VHa-. For VHa suppression a newborn a3/a3 rabbit was injected periodically with anti-VHa3 antiserum; when it was 2 months of age and its serum Ig was greater than 94% VHa-, cDNA clones were generated from splenic RNA. The nucleotide sequences of eight putative VHa(-)-encoding cDNA clones were compared to those of eight cDNA clones generated from RNA of non-suppressed a3/a3 rabbits. The presumed VHa3-encoding cDNA clones from the non-suppressed rabbits appeared to derive from VH1-a3, the 3'-most germline VH gene segment. In contrast, the VHa(-)-encoding cDNA clones from the suppressed rabbit were distinctly different from VH1 and were most probably derived from germline VH segments other than VH1. Because the expressed VHa- gene repertoire was highly restricted, we propose that VHa- molecules in a3/a3 rabbits may be derived from as few as three germline VH gene segments.
DiPietro
L A
LA
Department of Microbiology and Immunology, University of Illinois, Chicago 60680.
Sethupathi
P
P
Kingzette
M
M
Zhai
S K
SK
Suter
M
M
Knight
K L
KL
D000595:Amino Acid Sequence; D000818:Animals; D000916:Antibody Diversity / Q000235:genetics; D001483:Base Sequence; D004247:DNA / Q000235:genetics*; D005803:Genes, Immunoglobulin; D007126:Immunoglobulin Allotypes / Q000235:genetics*; D007165:Immunosuppression Therapy; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits
D007126:Immunoglobulin Allotypes; D012333:RNA, Messenger; D004247:DNA