ICAM-1 (CD54) expression on B lymphocytes is associated with their costimulatory function and can be increased by coactivation with IL-1 and IL-7.
Recent studies have demonstrated that acute lymphoblastic leukemia-derived pre-B cell lines are deficient in their costimulatory function for T cell proliferation in response to the mitogen Con A and the superantigens TSST-1 and SEB. Stimulation of these pre-B cells with IL-7 increased their costimulatory function which involved the B7/CD28 pathway. In the present study, we stimulated T cells with Con A, TSST-1, and SEB in the presence of peripheral blood B lineage cells that do not constitutively express B7/BB1 on their surface and investigated whether their costimulatory function could also be enhanced by IL-7. We found that, in the presence of IL-1, stimulation with IL-7 increased the costimulatory function of B cells and their surface expression level of ICAM-1 (CD54). We then investigated whether costimulatory B cell function could be inhibited by blocking the ICAM-1/LFA-1 pathway. Addition of anti-ICAM-1 mAb to the coculture of T and B cells inhibited T cell proliferation by approximately 20%. In contrast, addition of anti-LFA-1 beta (CD18) mAb, directed against the T cell ligand of ICAM-1, inhibited T cell proliferation almost completely. To determine the role of ICAM-1 in costimulatory B cell function, we sorted B cells into ICAM-1low-and ICAM-1high-expressing populations. We found that B cells expressing high levels of surface ICAM-1 elicited significantly higher T cell responses than those with low levels, suggesting that the expression level of ICAM-1 on peripheral blood B cells correlates with their costimulatory function.
Dennig
D
D
Department of Pediatrics, Sloan-Kettering Institute, New York, New York 10021.
Lacerda
J
J
Yan
Y
Y
Gasparetto
C
C
O'Reilly
R J
RJ
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D015851:Interleukin-7 / Q000008:administration & dosage / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D015851:Interleukin-7; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1