Regulation of VH-gene expression is a lineage-specific developmental marker

We have previously shown that in IgH congenic mice V_H-gene family usage in neonatal spleen B cells and adult Ig-secreting cells is entirely determined by the IgH locus, while in adult resting B cells it is regulated by genetic element(s) located outside the IgH locus. Two observations reported here demonstrate that the differential expression of V_H genes is an intrinsic property of the respective cell populations, determined by both the IgH locus and by a cis element(s) operating independently in the same animal. First, the study of F1 hybrids between the IgH congenic B6^a and CB.20 strains demonstrates that cis elements control V_H-gene family expression. Second, studies in irradiation chimeras showed that the environment in which cell differentiation proceeds is unable to overcome those controls. In chimeras of IgH congenic donors, V_H-gene expression in fetal liver-derived splenic B cells and Ig-secreting cells is dictated by the IgH haplotype, while in bone marrow-derived B cells is entirely determined by the cis element(s). These results show a developmental and cell lineage-related restriction in V_H-gene expression, and suggest that most adult splenic Ig-secreting cells may originate from precursors originally present in fetal liver, but which are rare among adult bone marrow precursors and CD5⁺ B cells.