Sex-associated differences in the immune response against fetal major histocompatibility antigens

Alloantibodies against H-2^b and H-2^k haplotypes were produced in C57BL/6J and C3H female and male mice in response to transplantation of F₁ fetal tissue (bone) or adult F₁ cells (spleen). Testing IgG1 and IgG2 antibodies by means of the fluorescence-activated cell sorter (FACS II), we found no differences between males and females in the isotype content of antisera produced against spleen cells from adult donors. In contrast, striking sex-associated differences were found in the isotypes produced against fetal allografts: females produced much more IgG1 than males, although they produced comparable amounts of IgG2. Hence, it appears that females differ from males in their humoral alloreactivity against major histocompatibility complex (MHC) gene products expressed on fetal cells. Such MHC antigens expressed on fetal tissues seem to generate different immune signals than the MHC antigens expressed on adult cells. These observations might be of relevance to the biological role played by the IgG1 alloantibodies produced during pregnancy against the MHC alloantigens of the fetus.