Regulation of B cell precursor proliferation by aminopeptidase A.
The BP-1/6C3 molecule expressed by early B lineage cells and some stromal cells has been identified as aminopeptidase A (APA). We have previously demonstrated that IL-7 selectively induces BP-1/APA expression by pre-B cells coincident with their growth. Here we directly demonstrate that BP-1 is preferentially expressed by the proliferating subpopulation of normal B cell progenitors. Furthermore, when non-adherent BALB/c bone marrow cells were incubated with IL-7 in the presence of purified BP-1 antibody, B cell precursor proliferation was markedly inhibited. Modulation of the BP-1/6C3 antigen did not occur in the presence of the BP-1 antibody, but APA enzymatic activity was significantly inhibited. The 6C3 antibody, which recognizes a different epitope on the APA molecule, had no effect on either B cell precursor proliferation or APA enzyme activity. We hypothesized that neutralization of APA by the BP-1 antibody results in inhibition of IL-7 driven B cell precursor proliferation. However, when isolated 14.8+ bone marrow cells were cultured with IL-7 in the presence of the BP-1 antibody, no inhibition of proliferation occurred. This data suggested that the effect of the BP-1 antibody might be related to the action of APA on peptides in the marrow microenvironment which are not present in cultures of isolated B cell precursors. The addition of irradiated non-adherent bone marrow cells to the 14.8+ cell cultures restored the inhibitory effect of the BP-1 antibody. Based on these observations, we propose that APA cleaves a small peptide which serves as a natural inhibitor of B cell precursor proliferation.
Welch
P A
PA
Department of Pediatrics, University of Alabama, Birmingham 35294, USA.
D000626:Aminopeptidases / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000502:physiology; D000804:Angiotensin II / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000937:Antigen-Antibody Reactions; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002766:Cholecystokinin / Q000276:immunology; D043384:Glutamyl Aminopeptidase; D006131:Growth Inhibitors / Q000276:immunology; D006133:Growth Substances / Q000276:immunology* / Q000502:physiology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D015032:Zinc / Q000276:immunology
D000911:Antibodies, Monoclonal; D006131:Growth Inhibitors; D006133:Growth Substances; D007166:Immunosuppressive Agents; D015851:Interleukin-7; D000804:Angiotensin II; D002766:Cholecystokinin; D000626:Aminopeptidases; D043384:Glutamyl Aminopeptidase; C062906:BP-1-6C3 antigen; D008666:Metalloendopeptidases; D015032:Zinc