TY - JOUR
T1 - SWAP-70 deficiency causes high-affinity plasma cell generation despite impaired germinal center formation
AU - Quemeneur, Laurence
AU - Angeli, Veronique
AU - Chopin, Michael
AU - Jessberger, Rolf
PY - 2008/3/1
Y1 - 2008/3/1
N2 - 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 ex-trafollicular generation of high-affinity plasma cells, but does not adequately support the memory response.
AB - 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 ex-trafollicular generation of high-affinity plasma cells, but does not adequately support the memory response.
UR - http://www.scopus.com/inward/record.url?scp=41949123665&partnerID=8YFLogxK
U2 - 10.1182/blood-2007-07-102822
DO - 10.1182/blood-2007-07-102822
M3 - Article
C2 - 18094331
AN - SCOPUS:41949123665
SN - 0006-4971
VL - 111
SP - 2714
EP - 2724
JO - Blood
JF - Blood
IS - 5
ER -