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 Blood, 1 March 2008, Vol. 111, No. 5, pp. 2714-2724.
Prepublished online as a Blood First Edition Paper on December 19, 2007; DOI 10.1182/blood-2007-07-102822.

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IMMUNOBIOLOGY

SWAP-70 deficiency causes high-affinity plasma cell generation despite impaired germinal center formation

Laurence Quemeneur1, Veronique Angeli1, Michael Chopin2, and Rolf Jessberger1,2

1 Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY; and 2 Institute of Physiological Chemistry, Dresden University of Technology, Dresden, Germany

Germinal centers (GCs) are lymphoid tissue structures central to the generation of long-lived, high-affinity, antibody-forming B cells. However, induction, maintenance, and regulation of GCs are not sufficiently understood. The F-actin–binding, Rac-interacting protein SWAP-70 is strongly expressed in activated B cells like those in B follicles. Recent work suggests that SWAP-70 is involved in B-cell activation, migration, and homing. Therefore, we investigated the role of SWAP-70 in the T-dependent immune response, in GC formation, and in differentiation into plasma and memory B cells. Compared with wt, sheep red blood cell (SRBC)–, or NP-KLH–immunized SWAP-70–/– mice have strongly reduced numbers of GCs and GC-specific B cells. However, SWAP-70–/– NP-specific B cells accumulate outside of the B follicles, and SWAP-70–/– mice show more plasma cells in the red pulp and in the bone marrow, and increased NP-specific Ig and antibody-forming B cells. Yet the memory response is impaired. Thus, SWAP-70 deficiency uncouples GC formation from T-dependent antibody and long-lived plasma cell production and causes extrafollicular generation of high-affinity plasma cells, but does not adequately support the memory response.


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