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Cellular interaction in germinal centers. Roles of CD40 ligand and B7-2 in established germinal centers.

S Han, K Hathcock, B Zheng, T B Kepler, R Hodes and G Kelsoe
J Immunol July 15, 1995, 155 (2) 556-567;
S Han
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K Hathcock
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B Zheng
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T B Kepler
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R Hodes
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G Kelsoe
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Abstract

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.

  • Copyright © 1995 by American Association of Immunologists
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The Journal of Immunology
Vol. 155, Issue 2
15 Jul 1995
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Cellular interaction in germinal centers. Roles of CD40 ligand and B7-2 in established germinal centers.
S Han, K Hathcock, B Zheng, T B Kepler, R Hodes, G Kelsoe
The Journal of Immunology July 15, 1995, 155 (2) 556-567;

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Cellular interaction in germinal centers. Roles of CD40 ligand and B7-2 in established germinal centers.
S Han, K Hathcock, B Zheng, T B Kepler, R Hodes, G Kelsoe
The Journal of Immunology July 15, 1995, 155 (2) 556-567;
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