Constitutive CD40L expression on B cells prematurely terminates germinal center response and leads to augmented plasma cell production in T cell areas

A Bolduc, E Long, D Stapler, M Cascalho… - The Journal of …, 2010 - journals.aai.org
A Bolduc, E Long, D Stapler, M Cascalho, T Tsubata, PA Koni, M Shimoda
The Journal of Immunology, 2010journals.aai.org
Abstract CD40/CD40L engagement is essential to T cell-dependent B cell proliferation and
differentiation. However, the precise role of CD40 signaling through cognate T–B interaction
in the generation of germinal center and memory B cells is still incompletely understood. To
address this issue, a B cell-specific CD40L transgene (CD40LBTg) was introduced into mice
with B cell-restricted MHC class II deficiency. Using this mouse model, we show that
constitutive CD40L expression on B cells alone could not induce germinal center …
Abstract
CD40/CD40L engagement is essential to T cell-dependent B cell proliferation and differentiation. However, the precise role of CD40 signaling through cognate T–B interaction in the generation of germinal center and memory B cells is still incompletely understood. To address this issue, a B cell-specific CD40L transgene (CD40LBTg) was introduced into mice with B cell-restricted MHC class II deficiency. Using this mouse model, we show that constitutive CD40L expression on B cells alone could not induce germinal center differentiation of MHC class II-deficient B cells after immunization with T cell-dependent Ag. Thus, some other MHC class II-dependent T cell-derived signals are essential for the generation of germinal center B cells in response to T cell-dependent Ag. In fact, CD40LBTg mice generated a complex Ag-specific IgG1 response, which was greatly enhanced in early, but reduced in late, primary response compared with control mice. We also found that the frequency of Ag-specific germinal center B cells in CD40LBTg mice was abruptly reduced 1 wk after immunization. As a result, the numbers of Ag-specific IgG1 long-lived plasma cells and memory B cells were reduced. By histology, large numbers of Ag-specific plasma cells were found in T cell areas adjacent to Ag-specific germinal centers of CD40LBTg mice, temporarily during the second week of primary response. These results indicate that CD40L expression on B cells prematurely terminated their ongoing germinal center response and produced plasma cells. Our results support the notion that CD40 signaling is an active termination signal for germinal center reaction.
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