Anti-bacterial specificities in the human fetal B cell repertoire

To study the human fetal B cell repertoire, liver and spleen lymphocytes were fused with the human x mouse heteromyeloma line CB-F7. Initially, 2310 IgM and 181 IgG producing hybridoma lines were established. Culture supernatants were analysed for binding activity to antigens from both the exogeneous and the endogeneous environments. For IgG secreting cell lines no antigenetic specificity has been detected. However, independently from the gestational age, monoclonal IgM antibodies binding to bacterial antigens (tetanus toxoid, lipid A, N. meningitidis antigens) were found. In particular, nearly 10% of the hybridomas obtained from fetal liver produced antibodies binding to lipid A (endotoxin). Among the IgM antibodies with anti-bacterial specificities approximately 30% were found to be polyspecific, i.e. these antibodies recognized auto-antigens of different molecular origin as well (ssDNA, keratin, myosin, actin). We conclude that polyreactive natural IgM antibodies may be generated during fetal life, which may take part in the formation of a humoral anti-infectious first line defense barrier in the neonate.