Genetic analysis of the maternally induced affinity enhancement in the non-Ox1 idiotypic antibody repertoire of the primary immune response to 2-phenyloxazolone

The early phases of ontogeny are decisive for the development of the B-cell repertoire. Here, we demonstrate that maternal tertiary immunization of BA LB/c mice with 2-phenyloxazolone (phOx) caused a drastic alteration of the primary antigen-specific repertoire of the offspring. Maternal tertiary imm unization or quaternary antibodies, which exhibited an extremely weak cross -reactivity with the major Ox1 idiotype (Id(Ox1)), induced a change in the proportion of Id(Ox1)/non-Id(Ox1) antiphOx antibodies in the F1 and F2 prim ary repertoire. The observed variability in the level of IdOx(1) expression (10-90%) exceeded even the seemingly genetically based differences between various mouse strains. In comparison with the non-Id(Ox1) of control mice, half of the non-Id(Ox1) antibodies showed a 5-100-fold enhanced affinity. Sixty per cent of these antibodies exhibited an affinity identical to that of Id(Ox1) antibodies, which are normally of the highest affinity, while th e remaining 40% exceeded even that of Id(Ox1) by a factor of 10. The non-Id (Ox1) were encoded by V-H/V-L genes and/or combinations thereof which are e ither new, hitherto unobserved in the antiphOx response, or typical of memo ry responses in normal mice. The significance of these data is discussed wi th respect to the possibility that maternal antibodies, which are acquired through multiple immune maturation processes, may have an epigenetic (non-M endelian) inheritable potential for the offspring.