CD11c Expression Identifies a Population of Extrafollicular Antigen-Specific Splenic Plasmablasts Responsible for CD4 T-Independent Antibody Responses during Intracellular Bacterial Infection

Racine, Rachael; Chatterjee, Mary; Winslow, Gary M.

doi:10.4049/jimmunol.181.2.1375

Cited by 88 publications

(118 citation statements)

References 84 publications

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“…Cells with classic features of B cells and DCs can develop from B-cell progenitors (34). Plasmablasts in splenic extrafollicular regions that promote T-independent humoral responses also expressed CD11c, albeit at lower levels than IDO-competent cells (35). However, it is unclear whether CD11c + B cells were IDO-competent.…”

Section: Discussionmentioning

confidence: 99%

B-lymphoid cells with attributes of dendritic cells regulate T cells via indoleamine 2,3-dioxygenase

Johnson¹,

Kahler²,

Baban³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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A discrete population of splenocytes with attributes of dendritic cells (DCs) and coexpressing the B-cell marker CD19 is uniquely competent to express the T-cell regulatory enzyme indoleamine 2,3-dioxygenase (IDO) in mice treated with TLR9 ligands (CpGs). Here we show that IDO-competent cells express the B-lineage commitment factor Pax5 and surface immunoglobulins. CD19 ablation abrogated IDO-dependent T-cell suppression by DCs, even though cells with phenotypic attributes matching IDO-competent cells developed normally and expressed IDO in response to interferon γ. Consequently, DCs and regulatory T cells (Tregs) did not acquire T-cell regulatory functions after TLR9 ligation, providing an alternative perspective on the known T-cell regulatory defects of CD19-deficient mice. DCs from B-cell-deficient mice expressed IDO and mediated T-cell suppression after TLR9 ligation, indicating that B-cell attributes were not essential for B-lymphoid IDO-competent cells to regulate T cells. Thus, IDO-competent cells constitute a distinctive B-lymphoid cell type with quintessential T-cell regulatory attributes and phenotypic features of both B cells and DCs. B cells | T-cell regulation | CD19I ndoleamine 2,3-dioxygenase (IDO) is an intracellular enzyme expressed in response to interferons (IFNs) at sites of inflammation. IDO inhibitors exacerbated T-cell-mediated pathology in models of tumor growth and autoimmune, infectious, and allergic diseases, and are currently under evaluation as potential tumor vaccine adjuvants in clinical settings (1, 2). By analogy to the tumor-protective effects of IDO, some pathogens may exploit IDO to facilitate persistence and IDO may attenuate vaccine-induced immunity (3-6). Consistent with this paradigm, artificially enhanced IDO activity attenuated graft versus host disease after bone marrow engraftment and prolonged rat lung allograft survival (7-9). Thus, IDO-dependent T-cell regulation occurs in multiple settings of chronic inflammation relevant to clinical syndromes.Despite the potential benefits of manipulating IDO activity to improve therapy in chronic inflammatory syndromes, little is known about the cellular basis of IDO-mediated T-cell regulation in physiologic settings. Antigen presenting cells (APCs) expressing IDO, such as dendritic cells (DCs), activate regulatory T cells (Tregs) and directly suppress effector T cells at sites of tissue inflammation (10, 11). Cells with functional and phenotypic attributes of DCs in mice and humans are competent to express IDO and regulate T-cell responses (11-15). In mice, splenocytes uniquely competent to mediate T-cell suppression via IDO after in vivo treatment with TLR9 ligands (CpGs) were a rare cell type located in splenic red pulp with phenotypic attributes of DCs (CD11c, CD8α, CD80/86, MHCII). IDO-competent cells also expressed B220 and the B-cell lineage marker CD19, but not the plasmacytoid DC (pDC) marker PDCA/120G8 (13). After CTLA4-Ig and CpG treatment, IDO-competent cells produced IFNα (15, 16), a functional attribute of pDCs and ...

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Section: Discussionmentioning

confidence: 99%

B-lymphoid cells with attributes of dendritic cells regulate T cells via indoleamine 2,3-dioxygenase

Johnson¹,

Kahler²,

Baban³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…ϩ and CD40L in Splenic T Cells-HSP70 expression in murine splenic CD11c high cells are predominatly DC (Ͼ90%) (31). These cells were identified with PE-labeled anti-CD11c mAb.…”

Section: Assay Of Hsp70 and Mail-15 In Murine Cd11cmentioning

confidence: 99%

A Comparative Study of Stress-mediated Immunological Functions with the Adjuvanticity of Alum

Wang

Rahman

Lehner

2012

Journal of Biological Chemistry

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Background: Alum and stress agents induce inflammasomes. The hypothesis was examined whether HSP70, a hallmark of cell stress, is involved both in alum and stress-mediated adjuvanticity. Results: Alum induced HSP70-dependent adjuvanticity as did the three stress agents. Conclusion: Inducible HSP70 is involved both in stress and alum-mediated adjuvant functions. Significance: Stress agents may provide an alternative strategy in developing novel adjuvants enhancing immunity.

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“…The location and cell types inherent in the EF response suggest that it may be regulated quite differently from the GC response and may generate different cellular products with different biological implications. The EF pathway is seen transiently in T cell-dependent responses to protein antigens (Ags) (1) and more recently has been appreciated as a major and sometimes sustained component of pathogen responses, particularly to bacteria (2,3).…”

mentioning

confidence: 99%

Facultative role for T cells in extrafollicular Toll-like receptor-dependent autoreactive B-cell responses in vivo

Sweet

Ols

Cullen

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Extrafollicular (EF) B-cell responses are increasingly being recognized as an alternative pathway of B-cell activation, particularly in autoimmunity. Critical cellular interactions required for the EF Bcell response are unclear. A key question in autoimmunity, in which Toll-like receptor (TLR) signals are costimulatory and could be sufficient for B-cell activation, is whether T cells are required for the response. This is pivotal, because autoreactive B cells are considered antigen-presenting cells for autoreactive T cells, but where such interactions occur has not been identified. Here, using AM14 site-directed transgenic rheumatoid factor (RF) mice, we report that B cells can be activated, differentiate, and isotypeswitch independent of antigen-specific T-cell help, αβ T cells, CD40L signaling, and IL-21 signaling to B cells. However, T cells do dramatically enhance the response, and this occurs via CD40L and IL-21 signals. Surprisingly, the response is completely inducible T-cell costimulator ligand independent. These results establish that, although not required, T cells substantially amplify EF autoantibody production and thereby implicate T-independent autoreactive B cells as a potential vector for breaking T-cell tolerance. We suggest that these findings explain why autoreactivity first focuses on self-components for which B cells carry TLR ligands, because these will uniquely be able to activate B cells independently of T cells, with subsequent T-B interactions activating autoreactive T cells, resulting in chronic autoimmunity.systemic lupus | autoantibodies

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CD11c Expression Identifies a Population of Extrafollicular Antigen-Specific Splenic Plasmablasts Responsible for CD4 T-Independent Antibody Responses during Intracellular Bacterial Infection

Cited by 88 publications

References 84 publications

B-lymphoid cells with attributes of dendritic cells regulate T cells via indoleamine 2,3-dioxygenase

B-lymphoid cells with attributes of dendritic cells regulate T cells via indoleamine 2,3-dioxygenase

A Comparative Study of Stress-mediated Immunological Functions with the Adjuvanticity of Alum

Facultative role for T cells in extrafollicular Toll-like receptor-dependent autoreactive B-cell responses in vivo

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