B cell receptor and Toll-like receptor signaling coordinate to control distinct B-1 responses to both self and the microbiota. 2019

Lieselotte Sm Kreuk, and Meghan A Koch, and Leianna C Slayden, and Nicholas A Lind, and Sophia Chu, and Hannah P Savage, and Aaron B Kantor, and Nicole Baumgarth, and Gregory M Barton
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.

B-1a cells play an important role in mediating tissue homeostasis and protecting against infections. They are the main producers of 'natural' IgM, spontaneously secreted serum antibodies predominately reactive to self antigens, like phosphatidylcholine (PtC), or antigens expressed by the intestinal microbiota. The mechanisms that regulate the B-1a immunoglobulin (Ig) repertoire and their antibody secretion remain poorly understood. Here, we use a novel reporter mouse to demonstrate that production of self- and microbiota-reactive antibodies is linked to BCR signaling in B-1a cells. Moreover, we show that Toll-like receptors (TLRs) are critical for shaping the Ig repertoire of B-1a cells as well as regulating their antibody production. Strikingly, we find that both the colonization of a microbiota as well as microbial-sensing TLRs are required for anti-microbiota B-1a responses, whereas nucleic-acid sensing TLRs are required for anti-PtC responses, demonstrating that linked activation of BCR and TLRs controls steady state B-1a responses to both self and microbiota-derived antigens.

UI MeSH Term Description Entries
D007155 Immunologic Factors Biologically active substances whose activities affect or play a role in the functioning of the immune system. Biological Response Modifier,Biomodulator,Immune Factor,Immunological Factor,Immunomodulator,Immunomodulators,Biological Response Modifiers,Biomodulators,Factors, Immunologic,Immune Factors,Immunological Factors,Modifiers, Biological Response,Response Modifiers, Biological,Factor, Immune,Factor, Immunological,Factors, Immune,Factors, Immunological,Modifier, Biological Response,Response Modifier, Biological
D011947 Receptors, Antigen, B-Cell IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment. Antigen Receptors, B-Cell,B-Cell Antigen Receptor,B-Cell Antigen Receptors,Surface Immunoglobulin,Immunoglobulins, Membrane-Bound,Immunoglobulins, Surface,Membrane Bound Immunoglobulin,Membrane-Bound Immunoglobulins,Receptors, Antigen, B Cell,Surface Immunoglobulins,Antigen Receptor, B-Cell,Antigen Receptors, B Cell,B Cell Antigen Receptor,B Cell Antigen Receptors,Bound Immunoglobulin, Membrane,Immunoglobulin, Membrane Bound,Immunoglobulin, Surface,Immunoglobulins, Membrane Bound,Membrane Bound Immunoglobulins,Receptor, B-Cell Antigen,Receptors, B-Cell Antigen
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001324 Autoantigens Endogenous tissue constituents with the ability to interact with AUTOANTIBODIES and cause an immune response. Autoantigen,Autologous Antigen,Autologous Antigens,Self-Antigen,Self-Antigens,Antigen, Autologous,Antigens, Autologous,Self Antigen,Self Antigens
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D016175 B-Lymphocyte Subsets A classification of B-lymphocytes based on structurally or functionally different populations of cells. B-Cell Subsets,Tumor-Infiltrating B Cells,Tumor-Infiltrating B Lymphocytes,B Effector 1 Cells,B Effector 2 Cells,B-1 Cells,B-1 Lymphocytes,B-2 Lymphocytes,B-Lymphocytes, Effector,B1 Lymphocytes,B2 Lymphocytes,Be1 Cells,Be2 Cells,Effector B Cells,B 1 Cells,B 1 Lymphocytes,B 2 Lymphocytes,B Cell Subsets,B Cell, Tumor-Infiltrating,B Lymphocyte Subsets,B Lymphocyte, Tumor-Infiltrating,B-1 Cell,B-1 Lymphocyte,B-2 Lymphocyte,B-Cell Subset,B-Lymphocyte Subset,B-Lymphocyte, Effector,B1 Lymphocyte,B2 Lymphocyte,Be1 Cell,Be2 Cell,Cell, B-1,Cell, Be1,Cell, Be2,Effector B Cell,Effector B-Lymphocyte,Effector B-Lymphocytes,Lymphocyte, B-1,Lymphocyte, B-2,Lymphocyte, B1,Lymphocyte, B2,Tumor Infiltrating B Cells,Tumor Infiltrating B Lymphocytes,Tumor-Infiltrating B Cell,Tumor-Infiltrating B Lymphocyte
D051193 Toll-Like Receptors A family of pattern recognition receptors characterized by an extracellular leucine-rich domain and a cytoplasmic domain that share homology with the INTERLEUKIN 1 RECEPTOR and the DROSOPHILA toll protein. Following pathogen recognition, toll-like receptors recruit and activate a variety of SIGNAL TRANSDUCING ADAPTOR PROTEINS. Receptors, Toll-Like,Toll-Like Receptor,Receptor, Toll-Like,Receptors, Toll Like,Toll Like Receptor,Toll Like Receptors
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D051562 Proto-Oncogene Proteins c-bcr A serine-threonine kinase that contains a C2 DOMAIN and PLECKSTRIN HOMOLOGY DOMAIN. It also has activity as a GTPASE-ACTIVATING PROTEIN for RAC1 PROTEIN and CDC42 PROTEIN. It functions as a negative regulator of CELL PROLIFERATION and NEOPLASTIC CELL TRANSFORMATION and is commonly fused with cellular abl protein to form BCR-ABL FUSION PROTEINS in PHILADELPHIA CHROMOSOME positive LEUKEMIA patients. bcr Proto-Oncogene Proteins,c-bcr Proteins,Breakpoint Cluster Region Protein,Proto-Oncogene Protein bcr,Proto-Oncogene Protein c-bcr,c-bcr Proto-Oncogene Proteins,Proto Oncogene Protein bcr,Proto Oncogene Protein c bcr,Proto Oncogene Proteins c bcr,Proto-Oncogene Proteins, bcr,Proto-Oncogene Proteins, c-bcr,bcr Proto Oncogene Proteins,c bcr Proteins,c bcr Proto Oncogene Proteins,c-bcr, Proto-Oncogene Protein,c-bcr, Proto-Oncogene Proteins
D064307 Microbiota The full collection of microbes (bacteria, fungi, virus, etc.) that naturally exist within a particular biological niche such as an organism, soil, a body of water, etc. Human Microbiome,Microbiome,Microbiome, Human,Microbial Community,Microbial Community Composition,Microbial Community Structure,Community Composition, Microbial,Community Structure, Microbial,Community, Microbial,Composition, Microbial Community,Human Microbiomes,Microbial Communities,Microbial Community Compositions,Microbial Community Structures,Microbiomes,Microbiotas

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