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CD19 and CD32b Differentially Regulate Human B Cell Responsiveness

CD19 and CD32b Differentially Regulate Human B Cell Responsiveness

Jodi L Karnell, Nazzareno Dimasi, Fredrick G Karnell 3rd, Ryan Fleming, Ellen Kuta, Mildred Wilson, Herren Wu, Changshou Gao, Ronald Herbst, Rachel Ettinger

J Immunol. 2014 Feb 15;192(4):1480-90.

PMID: 24442430

Abstract:

B cell activation is regulated by a variety of signals. CD19 positively regulates B cell activation, augmenting signals delivered through the BCR complex. In contrast, CD32b contains an ITIM and negatively regulates BCR signaling. Importantly, there are drugs currently in clinical trials and preclinical development that cross-link CD32b to molecules within the BCR complex. We wanted to address how single engagement versus cotargeting these molecules affects human B cell function. When B cells from healthy individuals were activated by signals that mimic a T cell response (IL-21 costimulation), ligation of CD32b, but not CD19, inhibited B cell expansion and plasma cell (PC) differentiation. In contrast, when B cells were activated through TLR, anti-CD19, but not anti-CD32b, blunted the response. However, when both CD19 and CD32b were coengaged by a bispecific anti-CD19×CD32b Ab, both types of stimuli were potently inhibited. Cross-linking CD19 with CD32b also inhibited Ab-independent functions of B cells, such as HLA upregulation, cytokine production, and the ability of B cells to prime CD4(+) T cells. Finally, although cross-linking CD19 and CD32b inhibited PC differentiation of primary B cells, it did not alter Ig production from pre-established PCs. These data elucidate the mechanism by which a complex set of signals determines the fate of B cell responsiveness. Although signals through CD19 influence TLR-driven activation, CD32b impacts the magnitude of the response following IL-21 costimulation. Therefore, simultaneous targeting of multiple surface molecules may be a necessary approach to comprehensively modulate B cell activation in vivo.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413186	Fc-gamma RIIB/CD32b human			Price

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