Switch recombination in fetal porcine thymus is uncoupled from somatic mutation.

Since fetal serum Ig isotype profiles suggested that IgG and IgA could be of de novo origin, we studied their transcription and secretion. IgM transcripts were present at 50 days of gestation in major fetal lymphoid tissues, IgG and IgA transcription was pronounced at 60 days in fetal thymus and both transcription and secretion in this organ increased in late fetal life. The CDR3 spectratype of thymic IgG and IgA transcripts was as polyclonal as that of IgM already at 70 days in utero indicating a broad repertoire of switched B-cells. However, VDJs transcribed with the switched isotypes were not hypermutated as were those from immunized fetuses, indicating that switch recombination and somatic mutation are not coupled in utero in piglets. This finding and the fact that the oligoclonal IgA and IgM repertoires in a non-inductive site of the mucosal immune system (parotid gland) becomes polyclonal in piglets reared germ-free, suggest that initial expansion of switched B-cells in fetal and neonatal piglets is not driven by environmental antigen. Our findings collectively suggest that all IgA and IgM may result from de novo synthesis while some IgG probably results from selective transport. The latter is consistent with the gradual decline in serum IgG concentration in germ-free isolator piglets and the expression of FcRn in the porcine placenta.