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B cell receptor signal transduction in the GC is short-circuited by high phosphatase activity.
Khalil, Ashraf M; Cambier, John C; Shlomchik, Mark J.
Afiliação
  • Khalil AM; Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Science ; 336(6085): 1178-81, 2012 Jun 01.
Article em En | MEDLINE | ID: mdl-22555432
ABSTRACT
Germinal centers (GCs) generate memory B and plasma cells, which are essential for long-lived humoral immunity. GC B cells with high-affinity B cell receptors (BCRs) are selectively expanded. To enable this selection, BCRs of such cells are thought to signal differently from those with lower affinity. We show that, surprisingly, most proliferating GC B cells did not demonstrate active BCR signaling. Rather, spontaneous and induced signaling was limited by increased phosphatase activity. Accordingly, both SH2 domain-containing phosphatase-1 (SHP-1) and SH2 domain-containing inositol 5 phosphatase were hyperphosphorylated in GC cells and remained colocalized with BCRs after ligation. Furthermore, SHP-1 was required for GC maintenance. Intriguingly, GC B cells in the cell-cycle G(2) period regained responsiveness to BCR stimulation. These data have implications for how higher-affinity B cells are selected in the GC.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos B / Receptores de Antígenos de Linfócitos B / Centro Germinativo / Proteína Tirosina Fosfatase não Receptora Tipo 6 Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2012 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos B / Receptores de Antígenos de Linfócitos B / Centro Germinativo / Proteína Tirosina Fosfatase não Receptora Tipo 6 Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2012 Tipo de documento: Article