Many different levels of maturation and commitment are present in nontransformed cells identified serologically as...

The pre-B cell stage of B lymphocyte development is characterized by the presence of immunoglobulin heavy chains of the IgM isotype in the cytoplasm and no other heavy or light chains in the cytoplasm or on the surface. We established several cell lines that were identical in their serologically defined pre-B cell phenotypes and in their dependence upon interleukin 3 for growth, but which differed in their levels of cytoplasmic RNA from immunoglobulin constant region genes, in their rates of differentiation in vitro, and in the isotype profile of the antibodies that they secreted upon differentiation. The two cell lines that we have analyzed in detail, PF1 and PF1C, both contained RNA from the C mu and C delta heavy chain genes and from both the C kappa and C lambda light chain genes, even though they were not producing detectable polypeptide products from the C delta, C kappa, or C lambda genes. However, PF1C had higher levels of C gamma and C alpha RNA transcripts and differentiated in vitro under the influence of dendritic cells and T lymphocytes (DC-T) more rapidly than did PF1. If the DC-T were derived from spleens, all cell lines secreted only IgM. However, under the influence of DC-T from Peyer's patches PF1C secreted predominantly IgM, PF1 secreted primarily IgA, and a third line, PF3, secreted primarily IgG. Therefore, within the population of cells described as pre-B cells on the basis of their immunoglobulin gene polypeptide products, there are subpopulations that probably represent different levels of maturation and different levels of commitment to particular pathways of B lymphocyte development.