B cell subsets in spleens of BALB/c mice: identification and isolation of MMTV-expressing and MMTV-responding subpopulations.

The DNA of BALB/c mice contains two genomic- and one subgenomic-size MMTV proviruses that appear to be preferentially expressed in their spleen cells, although intact MMTV virions cannot be detected in the tissues of these mice. This retrovirus antigen expression is restricted to a subpopulation of B lymphocytes, as determined by double label immunofluorescence studies. Nylon-adherent, SIg-positive spleen lymphocytes from BALB/c mice are capable of being stimulated by purified MMTV in lymphocyte transformation assays. Two possibilities were explored: the MMTV-positive cells are the responders to MMTV in the blastogenesis assay, or there exists two B lymphocyte subsets, one expressing the MMTV antigen(s) and the other responding to the virus. Depletion of MMTV-positive, nylon-adherent cells with anti-MMTV and complement resulted in no significant change in the blastogenesis to MMTV, indicating that the MMTV-negative lymphocytes are the responders in this reaction. These results were confirmed by positive selection experiments by using a fluorescence-activated cell sorter. Two populations of nylon-adherent cells, on the basis of the presence or absence of MMTV antigen in their surfaces, were obtained by a two-way sorting procedure and were used in lymphocyte transformation assays. MMTV-expressing lymphocytes were found to be nonresponsive to MMTV antigens, although high levels of [3H]thymidine incorporation were observed in the MMTV-negative, nylon-adherent cell cultures exposed to MMTV. These data indicate that in normal BALB/c mice, expression of endogeneous retrovirus genetic information is restricted to a nylon-adherent spleen cell subset that is different from the one responding in blastogenesis to the viral antigens.