Dendritic Cell-Dependent Inhibition of B Cell Proliferation Requires CD22

Abstract

Dendritic Cell-Dependent Inhibition of B Cell Proliferation Requires CD221 Lorna Santos,* Kevin E. Draves,† Mark Boton,‡ Prabhjit K. Grewal,‡ Jamey D. Marth,‡ and Edward A. Clark2*† Recent studies have shown that dendritic cells (DCs) regulate B cell functions. In this study, we report that bone marrow (BM)-derived immature DCs, but not mature DCs, can inhibit BCR-induced proliferation of B cells in a contact-dependent manner. This inhibition is overcome by treatment with BAFF and is dependent on the BCR coreceptor CD22; however, it is not dependent on expression of the CD22 glycan ligand(s) produced by ST6Gal-I sialyltransferase. We found that a second CD22 ligand (CD22L) is expressed on CD11c
splenic and BM-derived DCs, which does not contain ST6Gal-I-generated sialic acids and which, unlike the B cell-associated CD22L, is resistant to neuraminidase treatment and sodium metaperiodate oxidation. Exam- ination of splenic and BM B cell subsets in CD22 and ST6Gal-I knockout mice revealed that ST6Gal-I-generated B cell CD22L plays a role in splenic B cell development, whereas the maintenance of long-lived mature BM B cells depends only on CD22 and not on 2,6-sialic acids produced by ST6Gal-I. We propose that the two distinct CD22L have different functions. The 2,6-sialic acid-containing glycoprotein is important for splenic B cell subset development, whereas the DC-associated ST6Gal-I-independent CD22L may be required for the maintenance of long-lived mature B cells in the BM. The Journal of Immunology, 2008, 180: 4561–4569. T he role of dendritic cells (DCs)3 in Ag capture, process- ing, and presentation to T cells has been extensively stud- ied (1–3). Upon entry into lymph nodes (LNs), DCs cap- ture and process Ag and then migrate to T cell zones where they present the Ag to Th cells. The primed Th cells, in turn, induce B cell growth, differentiation, and Ab production through the release of cytokines and also through direct cell-cell contact requiring CD40-CD40L

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