Extracellular Signal-Regulated Protein Kinase 2 Is Required for Efficient Generation of B Cells Bearing Antigen-Specific Immunoglobulin G

Abstract

Activation of extracellular signal-regulated protein kinase (ERK) has been implicated in proliferation as well as differentiation in a wide variety of cell types. Using B-cell-specific gene-targeted mice, we report here that in T-cell-dependent immune responses, ERK2 is required to generate efficient immunoglobulin G (IgG) production. In its absence, the proportion of antigen-specific surface IgG1-bearing cells and the subsequent number of IgG1 antibody-secreting cells were decreased, despite apparently unimpaired class switch recombination. Notably, this defect was countered by overexpression of the antiapoptotic factor Bcl-2. Together, our results suggest that ERK2 plays a key role in efficient generation of antigen-specific IgG-bearing B cells by promoting their survival.

We thank members of the Kurosaki laboratory for helpful discussion. We also thank T. Kitamura for providing Plat E cells and K. Kinoshita and H. Nagaoka for providing the protocol for DC-PCR.

This work was supported by grants to T.K. from the Ministry of Education, Science, Sport, and Culture of Japan and from the Uehara Memorial Foundation.