Nontransformed pre-B cells were induced to differentiate in vitro along several different but predictable pathways with only dendritic cells (DC) and concanavalin A-stimulated T lymphocytes. DC-T from spleen induced secretion of only IgM, whereas DC-T from Peyer's patches induced high levels of IgA and intermediate levels of IgM and IgG. Both the isotype of antibody secreted and the extent of pre-B cell differentiation were determined by the lymphoid tissue source of DC, not of T cells. The pre-B cells synthesizing detectable levels of only the IgM heavy chain had cytoplasmic RNA transcripts from both light chain constant region genes and from the entire length of the heavy chain constant locus. In cells secreting IgM there were deletions in the DNA flanking the Cmu coding region.
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