Polyclonal activation of rat B cells. I. A single mitogenic signal can stimulate proliferation, but three signals are required for differentiation.
A water-soluble, proteinaceous preparation derived from the cell walls of Salmonella typhimurium Re mutants has recently been tested in our laboratory for its ability to act as a mitogen for rat lymphocytes. We have found this preparation (STM) to be a potent stimulator of B lymphocyte proliferation, as measured both by 3H-TdR incorporation and by cell cycle analysis performed with flow cytofluorometry. STM stimulates approximately 50% of rat B cells to enter cycle. Previous investigations by others have shown that at least two sets of signals are required for B cell differentiation; a) proliferation signals that may consist of both a stimulator of B cell conversion from G0 to G1 and growth factors, and b) differentiation signals that probably include at least two B cell differentiation factors (BCDF). When STM was tested in a differentiation system it did not drive purified B cells to differentiate to PFC, either alone or when supplemented with a supernatant from concanavalin A-stimulated spleen cells (CAS). However, when both CAS and dextran sulfate (DXS) were supplied to the STM-stimulated cells, a large number of PFC resulted. DXS does not act by stimulating an additional, CAS-responsive B cell subset, since it has only a marginal effect upon 3H-TdR uptake and does not increase the number of B cells in cycle when used together with STM. We postulate that the two agents may be acting sequentially: STM stimulates the B cells to proliferate, and DXS drives the proliferating cells to become responsive to CAS. This suggests that the signals for B cell differentiation must consist of at least three activities: a trigger to stimulate the cells to proliferate, a factor to drive the cells to a BCDF-responsive state, and a BCDF that can drive the cells to secrete antibody.
Stunz
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Feldbush
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D000818:Animals; D001402:B-Lymphocytes / Q000145:classification / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D002455:Cell Division; D016264:Dextran Sulfate; D003911:Dextrans / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D008934:Mitogens / Q000494:pharmacology*; D010641:Phenotype; D051381:Rats; D011917:Rats, Inbred Lew; D012486:Salmonella typhimurium / Q000276:immunology; D013936:Thymidine / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000494:pharmacology*
D003911:Dextrans; D008934:Mitogens; D000511:alpha-Macroglobulins; C032306:polyclonal B cell activator; D016264:Dextran Sulfate; D013936:Thymidine