title: Monoclonal antibodies to epitope of CD45R (B220) inhibit interleukin 4-mediated B cell proliferation and differentiation.
abstract: A mAb, ALP-2, produced by immunizing rats with proliferating lymph node cells from MRL/Mp-lpr/lpr mice, had an inhibitory effect on recombinant interleukin 4 (rIL-4)-mediated proliferation and differentiation of murine B cells. Kinetic analysis revealed that the ALP-2 exerted these inhibitory effects at an early phase of B cell proliferation and differentiation. Nevertheless, the proliferative response of thymocytes to rIL-4 was not inhibited by ALP-2. In addition, ALP-2 inhibited neither the B cell proliferation induced by interleukin 2 nor the B cell differentiation by interleukin 5. Cross-inhibition experiments, together with immunoblotting analysis, revealed that the LP-2 recognized by ALP-2 appears to be an epitope of CD45R (B220) molecule(s), the isoform(s) of the Ly-5 antigen system. Epitope mapping analysis using CD45 gene transfectants showed that Lp-2 epitope is dependent upon the expression of the first alternatively spliced exon of CD45 gene. Functional studies showed that the mAb to an epitope of CD45R, RA3-2C2, but not RA3-6B2, had similar inhibitory effects on the IL-4-mediated proliferative response of B cells. These findings suggest that the CD45R molecules associated with Lp-2 and RA3-2C2 epitopes are probably related to a signal transduction provided by IL-4 in B cells. The possibility that different pathways are operative for IL-4-mediated signaling between B and T cells has to be considered.
authors.affiliation: Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hasegawa
authors.forename: H
authors.initials: H
authors.lastname: Nishimura
authors.forename: S
authors.initials: S
authors.lastname: Ogawa
authors.forename: S
authors.initials: S
authors.lastname: Hirose
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Shirai
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000235:genetics; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D016207:Cytokines / Q000494:pharmacology; D004274:DNA, Recombinant; D000939:Epitopes; D006649:Histocompatibility Antigens / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000276:immunology* / Q000494:pharmacology; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D016207:Cytokines; D004274:DNA, Recombinant; D000939:Epitopes; D006649:Histocompatibility Antigens; D007074:Immunoglobulin G; D015847:Interleukin-4; D017493:Leukocyte Common Antigens