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One or more keywords matched the following properties of Clark, Marcus Ramsay
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overview Our laboratory has a long-standing interest in B cell antigen receptor (BCR) signaling and how BCR dependent processes regulate specific cell fate decisions. In the bone marrow, we have been working to understand how signals initiated through the pre-BCR, in conjunction with those delivered through the IL-7 receptor, coordinate cell cycle progression with immunoglobulin light chain gene recombination. These studies resulted in discovery of the epigenetic reader BRWD1 as critical for both regulating Ig-kappa accessibility and in coordinating broad transcriptional programs in early and late B lymphopoiesis. Recently, we have demonstrated that the pre-BCR initiates an IRF4-CXCR4 feedforward loop and that it is CXCR4 that directly signals Ig-kappa recombination. These latter findings fundamentally rewrite the canonical model of B lymphopoiesis. Furthermore, they are the first demonstration of a direct and independent role for CXCR4 in driving an important biological process. In the periphery, we have focused on the molecular control of germinal centers (GCs). Recently, we have recently defined two novel B cell populations within the dark zone that both allow compartmentalization of fundamental GC functions and reveal the molecular programs of the GC cycle. This new three population model fundamentally rewrites the GC paradigm. In all these areas, we have derived novel in vivo models, and have performed directed in vitro studies, to obtain definitive insights into these processes. Our translational studies have focused on how in situ adaptive immune responses drive tubulointerstitial inflammation in human lupus nephritis. For these studies, we have used deep machine learning to develop novel image analysis tools to quantify and identify functional relationships between different T cell and antigen presenting cell populations in situ. Remarkably, this bioinformatics platform approaches the sensitivity and specificity of two-photon excitation microscopy (TPEM). However, unlike TPEM, it can be applied to the study of human disease. We have also used single cell technologies to understand B cell selection at sites of inflammation and determine the interrelationships between transcriptional state and antigenic specificity.
One or more keywords matched the following items that are connected to Clark, Marcus Ramsay
Item TypeName
Concept Antigen-Antibody Complex
Concept Receptors, Antigen
Concept Receptors, Antigen, B-Cell
Concept Antigen Presentation
Concept Proliferating Cell Nuclear Antigen
Concept Receptors, Antigen, T-Cell
Academic Article The direct recruitment of BLNK to immunoglobulin alpha couples the B-cell antigen receptor to distal signaling pathways.
Academic Article Receptor-facilitated antigen presentation requires the recruitment of B cell linker protein to Igalpha.
Academic Article A point mutation in the constant region of Ig lambda1 prevents normal B cell development due to defective BCR signaling.
Academic Article Selection of B lymphocytes in the periphery is determined by the functional capacity of the B cell antigen receptor.
Academic Article B cell antigen receptor signaling and internalization are mutually exclusive events.
Academic Article HS1 functions as an essential actin-regulatory adaptor protein at the immune synapse.
Academic Article Regulation of lymphocyte progenitor survival by the proapoptotic activities of Bim and Bid.
Academic Article A self-reinforcing regulatory network triggered by limiting IL-7 activates pre-BCR signaling and differentiation.
Academic Article Ubiquitinylation of Ig beta dictates the endocytic fate of the B cell antigen receptor.
Academic Article Endocytic sequestration of the B cell antigen receptor and toll-like receptor 9 in anergic cells.
Academic Article Ikaros and Aiolos inhibit pre-B-cell proliferation by directly suppressing c-Myc expression.
Academic Article Igalpha: B all that you can B.
Academic Article The control and facilitation of MHC class II antigen processing by the BCR.
Academic Article Ig alpha and Ig beta are required for efficient trafficking to late endosomes and to enhance antigen presentation.
Academic Article The pre-B cell receptor in B cell development: recent advances, persistent questions and conserved mechanisms.
Academic Article PU.1 and Spi-B are required for normal B cell receptor-mediated signal transduction.
Academic Article Self-reactive IgE exacerbates interferon responses associated with autoimmunity.
Academic Article Bcl-2 as a Therapeutic Target in Human Tubulointerstitial Inflammation.
Academic Article EZH2 Regulates the Developmental Timing of Effectors of the Pre-Antigen Receptor Checkpoints.
Academic Article Igß ubiquitination activates PI3K signals required for endosomal sorting.
Academic Article CXCR4 signaling directs Igk recombination and the molecular mechanisms of late B lymphopoiesis.
Academic Article B-1a cells acquire their unique characteristics by bypassing the pre-BCR selection stage.
Academic Article Positive and negative selection shape the human naive B cell repertoire.
Academic Article Asymmetrical forward and reverse developmental trajectories determine molecular programs of B cell antigen receptor editing.
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  • B7 Antigens