B7-1 and B7-2 have overlapping, critical roles in immunoglobulin class switching and germinal center formation.
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.
Borriello
F
F
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Sethna
M P
MP
Boyd
S D
SD
Schweitzer
A N
AN
Tivol
E A
EA
Jacoby
D
D
Strom
T B
TB
Simpson
E M
EM
Freeman
G J
GJ
Sharpe
A H
AH
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
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