Stochastic pairing of heavy-chain and kappa light-chain variable gene families occurs in polyclonally activated B cells.
Frequencies of 25 immunoglobulin heavy-chain and kappa light-chain variable (VH + V kappa) gene-family pairings expressed in splenic B-cell populations were determined by hybridization of VH- and V kappa-family-specific DNA probes to mitogen-induced B-cell colonies from C57BL/6 mice or hybridomas derived from BALB/c and NZB mice. Both analyses support the conclusion that VH and V kappa gene families pair without bias; as would be expected for random association, the frequencies of specific VH + V kappa pairs may be estimated by the product of the independent VH and V kappa frequencies. Based upon the frequencies at which 9 VH and 12 V kappa gene families are expressed, we calculated the expected usage for approximately 100 VH + V kappa family pairings in neonatal and adult C57BL/6 mice. Variability in the expression of such VH + V kappa pairings is considerable; pairs representing greater than 10% to less than 0.01% of the splenic B-cell population occur. This variability is most pronounced in the neonate, where 6 VH + V kappa family pairs account for nearly 40% of all mitogen-reactive B cells. As the neonate matures, the distribution of frequencies for VH + V kappa pairings becomes more nearly uniform. This process may underlie the patterned acquisition of humoral immune responsiveness.
Kaushik
A
A
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029.
Schulze
D H
DH
Bonilla
F A
FA
Bona
C
C
Kelsoe
G
G
D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002999:Clone Cells; D015342:DNA Probes; D005803:Genes, Immunoglobulin; D006822:Hybrid Cells / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D005810:Multigene Family; D009693:Nucleic Acid Hybridization; D013154:Spleen / Q000276:immunology; D013269:Stochastic Processes
D015342:DNA Probes; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains