title: B7-1 and B7-2 have overlapping, critical roles in immunoglobulin class switching and germinal center formation.
abstract: Humoral immune responses were characterized in mouse strains lacking either or both B7 molecules. Mice deficient in both B7-1 and B7-2 failed to generate antigen-specific IgG1 and IgG2a responses and lacked germinal centers when immunized by a number of routes and even in the presence of complete Freund's adjuvant. These results demonstrate that B7-mediated signaling plays a critical role in germinal center formation and immunoglobulin class switching in vivo. Mice lacking only B7-1 or B7-2 mounted high-titer antigen-specific IgG responses when immunized in complete Freund's adjuvant, indicating that B7-1 and B7-2 can have overlapping, compensatory functions for IgG responses. When immunized intravenously without adjuvant, B7-2-deficient mice failed to switch antibody isotypes or form germinal centers, whereas B7-1-deficient mice gave antibody responses comparable with wild-type mice. Thus, B7-2 has an important role in initiating antibody responses in the absence of adjuvant, but the induction of B7-1 by adjuvant in B7-2-deficient mice can compensate for the absence of B7-2.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: F
authors.initials: F
authors.lastname: Borriello
authors.forename: M P
authors.initials: MP
authors.lastname: Sethna
authors.forename: S D
authors.initials: SD
authors.lastname: Boyd
authors.forename: A N
authors.initials: AN
authors.lastname: Schweitzer
authors.forename: E A
authors.initials: EA
authors.lastname: Tivol
authors.forename: D
authors.initials: D
authors.lastname: Jacoby
authors.forename: T B
authors.initials: TB
authors.lastname: Strom
authors.forename: E M
authors.initials: EM
authors.lastname: Simpson
authors.forename: G J
authors.initials: GJ
authors.lastname: Freeman
authors.forename: A H
authors.initials: AH
authors.lastname: Sharpe
mesh_terms: D000069594:Abatacept; D000276:Adjuvants, Immunologic / Q000737:chemistry; D000818:Animals; D000941:Antigens / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology*; D000943:Antigens, Differentiation / Q000096:biosynthesis; D000955:Antigens, T-Independent / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000502:physiology*; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; D005620:Freund's Adjuvant / Q000737:chemistry / Q000276:immunology; D018858:Germinal Center / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D018796:Immunoconjugates; D017578:Immunoglobulin Class Switching / Q000187:drug effects / Q000276:immunology*; D007141:Immunoglobulin Fc Fragments / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000955:Antigens, T-Independent; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D006241:Haptens; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments; D008562:Membrane Glycoproteins; C054401:trinitrophenyl keyhole limpet hemocyanin; D000069594:Abatacept; D005620:Freund's Adjuvant; D006433:Hemocyanins