최연수 교수

Follicular helper T cells (T(FH) cells) constitute the CD4(+) T cell subset that is specialized to provide help to germinal center (GC) B cells and, consequently, mediate the development of long-lived humoral immunity. T(FH) cell differentiation is driven by the transcription factor Bcl6, and recent studies have identified cytokine and cell-cell signals that drive Bcl6 expression. However, although T(FH) dysregulation is associated with several major autoimmune diseases, the mechanisms underlyin

Bcl6 is required for CD4 T cell differentiation into T follicular helper cells (Tfh). In this study, we examined the role of IL-6 in early processes of in vivo Tfh differentiation, because the timing and mechanism of action of IL-6 in Tfh differentiation have been controversial in vivo. We found that early Bcl6(+)CXCR5(+) Tfh differentiation was severely impaired in the absence of IL-6; however, STAT3 deficiency failed to recapitulate that defect. IL-6R signaling activates the transcription fact

B-1 cells are known to contribute most of the "natural antibodies" that are secreted in the steady state, antibodies which are crucial for protection against many pathogens including influenza virus. Whether the CD5(+) B-1a subset plays a role during an active immune response is incompletely understood. In contrast to recent data suggesting a passive role for B-1a cells, data provided here show strong highly localized activation of B-1 cells in the draining lymph nodes of the respiratory tract a

Follicular helper CD4 T (Tfh) cells are a distinct type of differentiated CD4 T cells uniquely specialized for B cell help. In this study, we examined Tfh cell fate commitment, including distinguishing features of Tfh versus Th1 proliferation and survival. Using cell transfer approaches at early time points after an acute viral infection, we demonstrate that early Tfh cells and Th1 cells are already strongly cell fate committed by day 3. Nevertheless, Tfh cell proliferation was tightly regulated

MicroRNAs (miRNAs) are small noncoding RNAs that act as potent regulators of gene expression. The discovery of miRNAs with specific temporal and spatial expression patterns revealed a hidden layer of post-transcriptional gene regulation. Furthermore, differential expression of miRNAs during disease progression identified miRNAs as relevant candidate genes in human pathologies. Currently the exact roles of miRNAs in human development and disease progression remain largely unknown. There have been

Natural IgM antibodies secreted in the absence of antigenic challenge are important contributors to antimicrobial immunity and tissue homeostasis. Early studies identified BM and, to a lesser extent the spleen, as main tissue sources of this spontaneously secreted IgM. However, the responsible B-cell subset has never been identified. Using multicolor flow cytometry, cell sorting and chimeric mice in which B-1 and B-2 cells and their secreted antibodies are distinguished by their Ig-allotype, we

To investigate the molecular and cellular mechanisms underlying the selection, differentiation, and apoptosis of germinal center (GC) B cells, we have established a culture system containing a follicular dendritic cell (FDC) line, HK. The mAb, 3C8, which is specific to HK cells and recognizes dendritic network in the GC, was developed and provided additional evidence that HK cells are related to FDC by sharing a unique surface Ag. The roles for CD40 ligand (CD40L) and T cell-derived cytokines in

Reciprocal interactions between B and follicular T helper (Tfh) cells orchestrate the germinal center (GC) reaction, a hallmark of humoral immunity. Abnormal GC responses could lead to the production of pathogenic autoantibodies and the development of autoimmunity. Here we show that miR-146a controls GC responses by targeting multiple CD40 signaling pathway components in B cells; by contrast, loss of miR-146a in T cells does not alter humoral responses. However, specific deletion of both miR-146

Follicular Th (T(FH)) cells are specialized in provision of help to B cells that is essential for promoting protective Ab responses. CD28/B7 (B7-1 and B7-2) interactions are required for germinal center (GC) formation, but it is not clear if they simply support activation of naive CD4 T cells during initiation of responses by dendritic cells or if they directly control T(FH) cells and/or directly influence follicular B cell differentiation. Using a model of vaccinia virus infection, we show that

Innate-like B-1a lymphocytes rapidly redistribute to regional mediastinal lymph nodes (MedLNs) during influenza infection to generate protective IgM. Here we demonstrate that influenza infection-induced type I interferons directly stimulate body cavity B-1 cells and are a necessary signal required for B-1 cell accumulation in MedLNs. Vascular mimetic flow chamber studies show that type I interferons increase ligand-mediated B-1 cell adhesion under shear stress by inducing high-affinity conformat