Stochastic pairing of heavy-chain and kappa light-chain variable gene families occurs in polyclonally activated B cells.

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Abstract
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. pairs may be estimated by the product of the independent VH and V.kappa. frequencies. Based upon the frequencies at which 9 VH and V.kappa. gene families are expressed, we calculated the expected usage for .apprxeq. 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 > 10% to < 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.