Cellular interaction in germinal centers. Roles of CD40 ligand and B7-2 in established germinal centers.
Costimulatory interactions between T and B lymphocytes are crucial for T cell activation and B cell proliferation and differentiation. We have compared the roles of CD40L and B7-2 in the initiation and maturation of humoral immunity by administering anti-CD40 ligand (L) or anti-B7-2 Ab during the early (days -1 to 3) or late (days 6-10) phases of primary responses to thymus-dependent (Td) and -independent (Ti) Ags. Germinal center (GC) formation in response to a Td Ag was inhibited completely by the early administration of anti-CD40L or anti-B7-2 Abs. Later in the response, established GCs remained sensitive to anti-CD40L but were resistant to treatment with anti-B7-2. However, Ig hypermutation was reduced dramatically in GCs of anti-B7-2-treated mice and humoral memory was impaired. Early administration of anti-CD40L reduced serum Ab levels to approximately 10% of controls, whereas early treatment with anti-B7-2 reduced Ab production by only 50%. Later treatments with either Ab had no effect on Ab production. Response to a type II Ti Ag was more resistant than Td responses to interruption of costimulatory interactions. Our findings suggest that the costimulatory roles of CD40:CD40L and B7-2:CD28/CTLA-4 differ in the GC; administration of anti-CD40L abrogates an established GC reaction, whereas Ab to B7-2 suppresses Ig hypermutation and entry into the B cell memory compartment. Once B cells have entered the differentiation pathway to Ab production, neither CD40L nor B7-2 is necessary for their continued differentiation and persistence.
Han
S
S
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore 21201, USA.
Hathcock
K
K
Zheng
B
B
Kepler
T B
TB
Hodes
R
R
Kelsoe
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology / Q000494:pharmacology*; D051940:B7-2 Antigen; D001428:Bacterial Vaccines / Q000276:immunology; D001483:Base Sequence; D023201:CD40 Ligand; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D007156:Immunologic Memory; D008024:Ligands; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D001428:Bacterial Vaccines; C497965:Cd86 protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand