PT  - JOURNAL ARTICLE
AU  - Han, S
AU  - Hathcock, K
AU  - Zheng, B
AU  - Kepler, T B
AU  - Hodes, R
AU  - Kelsoe, G
TI  - Cellular interaction in germinal centers. Roles of CD40 ligand and B7-2 in established germinal centers.
DP  - 1995 Jul 15
TA  - The Journal of Immunology
PG  - 556--567
VI  - 155
IP  - 2
4099  - http://www.jimmunol.org/content/155/2/556.short
4100  - http://www.jimmunol.org/content/155/2/556.full
SO  - J. Immunol.1995 Jul 15; 155
AB  - 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.