B Cell Receptor Signal Transduction in the GC Is Short-Circuited by High Phosphatase Activity

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Science  03 May 2012:
DOI: 10.1126/science.1213368

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Germinal centers (GCs) generate memory B and plasma cells, 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 SHP-1 and SHIP-1 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 G2 period regained responsiveness to BCR stimulation. These data have implications for how higher-affinity B cells are selected in the GC.

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