scholarly journals Physiological-Range Temperature Changes Modulate Cognate Antigen Processing and Presentation Mediated by Lipid Raft-Restricted Ubiquitinated B Cell Receptor Molecules

2010 ◽  
Vol 185 (9) ◽  
pp. 5032-5039 ◽  
Author(s):  
Bhuvana Katkere ◽  
Sarah Rosa ◽  
Adriana Caballero ◽  
Elizabeth A. Repasky ◽  
James R. Drake
Keyword(s):  
B Cell ◽  
Lipid Raft ◽  
Antigen Processing ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Temperature Changes ◽  
Physiological Range ◽  
Cognate Antigen ◽  
Antigen Processing And Presentation

scholarly journals Syk-dependent Actin Dynamics Regulate Endocytic Trafficking and Processing of Antigens Internalized through the B-Cell Receptor

2007 ◽  
Vol 18 (9) ◽  
pp. 3451-3462 ◽  
Author(s):  
Delphine Le Roux ◽  
Danielle Lankar ◽  
Maria-Isabel Yuseff ◽  
Fulvia Vascotto ◽  
Takeaki Yokozeki ◽  
...  
Keyword(s):  
B Cell ◽  
Antigen Processing ◽  
B Lymphocyte ◽  
Lymphocyte Activation ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Actin Dynamics ◽  
Endocytic Trafficking ◽  
Mhc Ii ◽  
Antigen Processing And Presentation

Antigen binding to the B-cell receptor (BCR) induces multiple signaling cascades that ultimately lead to B lymphocyte activation. In addition, the BCR regulates the key trafficking events that allow the antigen to reach endocytic compartments devoted to antigen processing, i.e., that are enriched for major histocompatibility factor class II (MHC II) and accessory molecules such as H2-DM. Here, we analyze the role in antigen processing and presentation of the tyrosine kinase Syk, which is activated upon BCR engagement. We show that convergence of MHC II- and H2-DM–containing compartments with the vesicles that transport BCR-uptaken antigens is impaired in cells lacking Syk activity. This defect in endocytic trafficking compromises the ability of Syk-deficient cells to form MHC II-peptide complexes from BCR-internalized antigens. Altered endocytic trafficking is associated to a failure of Syk-deficient cells to properly reorganize their actin cytoskeleton in response to BCR engagement. We propose that, by modulating the actin dynamics induced upon BCR stimulation, Syk regulates the positioning and transport of the vesicles that carry the molecules required for antigen processing and presentation.

scholarly journals Actin-Binding Protein 1 Regulates B Cell Receptor-Mediated Antigen Processing and Presentation in Response to B Cell Receptor Activation

2008 ◽  
Vol 180 (10) ◽  
pp. 6685-6695 ◽  
Author(s):  
Olusegun O. Onabajo ◽  
Margaret K. Seeley ◽  
Amruta Kale ◽  
Britta Qualmann ◽  
Michael Kessels ◽  
...  
Keyword(s):  
B Cell ◽  
Antigen Processing ◽  
Binding Protein ◽  
Cell Receptor ◽  
Receptor Activation ◽  
B Cell Receptor ◽  
Actin Binding ◽  
Actin Binding Protein ◽  
Antigen Processing And Presentation

scholarly journals Delivery of B Cell Receptor–internalized Antigen to Endosomes and Class II Vesicles

1997 ◽  
Vol 186 (8) ◽  
pp. 1299-1306 ◽  
Author(s):  
James R. Drake ◽  
Paul Webster ◽  
John C. Cambier ◽  
Ira Mellman
Keyword(s):  
B Cells ◽  
B Cell ◽  
Antigen Processing ◽  
Specific Antigen ◽  
Cell Receptor ◽  
Class Ii ◽  
Time Frame ◽  
B Cell Receptor ◽  
Subcellular Compartment ◽  
Endocytic Vesicles

B cell receptor (BCR)-mediated antigen processing is a mechanism that allows class II–restricted presentation of specific antigen by B cells at relatively low antigen concentrations. Although BCR-mediated antigen processing and class II peptide loading may occur within one or more endocytic compartments, the functions of these compartments and their relationships to endosomes and lysosomes remain uncertain. In murine B cells, at least one population of class II– containing endocytic vesicles (i.e., CIIV) has been identified and demonstrated to be distinct both physically and functionally from endosomes and lysosomes. We now demonstrate the delivery of BCR-internalized antigen to CIIV within the time frame during which BCR-mediated antigen processing and formation of peptide–class II complexes occurs. Only a fraction of the BCR-internalized antigen was delivered to CIIV, with the majority of internalized antigen being delivered to lysosomes that are largely class II negative. The extensive colocalization of BCR-internalized antigen and newly synthesized class II molecules in CIIV suggests that CIIV may represent a specialized subcellular compartment for BCR-mediated antigen processing. Additionally, we have identified a putative CIIV-marker protein, immunologically related to the Igα subunit of the BCR, which further illustrates the unique nature of these endocytic vesicles.

scholarly journals Engagement of the Human Pre-B Cell Receptor Generates a Lipid Raft–Dependent Calcium Signaling Complex

Immunity ◽  
2000 ◽  
Vol 13 (2) ◽  
pp. 243-253 ◽  
Author(s):  
Beichu Guo ◽  
Roberta M Kato ◽  
Maria Garcia-Lloret ◽  
Matthew I Wahl ◽  
David J Rawlings
Keyword(s):  
Calcium Signaling ◽  
B Cell ◽  
Lipid Raft ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Signaling Complex

scholarly journals Lipid Raft-Independent B Cell Receptor-Mediated Antigen Internalization and Intracellular Trafficking

2003 ◽  
Vol 170 (2) ◽  
pp. 905-912 ◽  
Author(s):  
Michelle A. Putnam ◽  
Amy E. Moquin ◽  
Megan Merrihew ◽  
Christopher Outcalt ◽  
Emily Sorge ◽  
...  
Keyword(s):  
B Cell ◽  
Lipid Raft ◽  
Intracellular Trafficking ◽  
Cell Receptor ◽  
B Cell Receptor

scholarly journals Public Immunity: Evolutionary Spandrels for Pathway-Amplifying Protective Antibodies

2021 ◽  
Vol 12 ◽  
Author(s):  
Maya Sangesland ◽  
Daniel Lingwood
Keyword(s):  
B Cell ◽  
Humoral Immunity ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Antibody Responses ◽  
Antibody Repertoire ◽  
Protective Antibodies ◽  
Cognate Antigen ◽  
Rational Vaccine Design ◽  
Antigen Reactivity

Humoral immunity is seeded by affinity between the B cell receptor (BCR) and cognate antigen. While the BCR is a chimeric display of diverse antigen engagement solutions, we discuss its functional activity as an ‘innate-like’ immune receptor, wherein genetically hardwired antigen complementarity can serve as reproducible templates for pathway-amplifying otherwise immunologically recessive antibody responses. We propose that the capacity for germline reactivity to new antigen emerged as a set of evolutionary spandrels or coupled traits, which can now be exploited by rational vaccine design to focus humoral immunity upon conventionally immune-subdominant antibody targets. Accordingly, we suggest that evolutionary spandrels account for the necessary but unanticipated antigen reactivity of the germline antibody repertoire.

scholarly journals Using B cell receptor lineage structures to predict affinity

2020 ◽  
Vol 16 (11) ◽  
pp. e1008391
Author(s):  
Duncan K. Ralph ◽  
Frederick A. Matsen
Keyword(s):  
B Cell ◽  
Real Data ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Evolutionary Information ◽  
Additional Source ◽  
Link Type ◽  
The Family ◽  
Cognate Antigen ◽  
Generation Sequencing

We are frequently faced with a large collection of antibodies, and want to select those with highest affinity for their cognate antigen. When developing a first-line therapeutic for a novel pathogen, for instance, we might look for such antibodies in patients that have recovered. There exist effective experimental methods of accomplishing this, such as cell sorting and baiting; however they are time consuming and expensive. Next generation sequencing of B cell receptor (BCR) repertoires offers an additional source of sequences that could be tapped if we had a reliable method of selecting those coding for the best antibodies. In this paper we introduce a method that uses evolutionary information from the family of related sequences that share a naive ancestor to predict the affinity of each resulting antibody for its antigen. When combined with information on the identity of the antigen, this method should provide a source of effective new antibodies. We also introduce a method for a related task: given an antibody of interest and its inferred ancestral lineage, which branches in the tree are likely to harbor key affinity-increasing mutations? We evaluate the performance of these methods on a wide variety of simulated samples, as well as two real data samples. These methods are implemented as part of continuing development of the partis BCR inference package, available at https://github.com/psathyrella/partis. Comments Please post comments or questions on this paper as new issues at https://git.io/Jvxkn.

scholarly journals APEX2 proximity biotinylation reveals protein dynamics triggered by B cell receptor activation

2020 ◽  
Author(s):  
Luqman O Awoniyi ◽  
Vid Šuštar ◽  
Sara Hernández-Pérez ◽  
Marika Vainio ◽  
Alexey V Sarapulov ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Lipid Raft ◽  
Cell Activation ◽  
Kinetic Resolution ◽  
Cell Receptor ◽  
Receptor Activation ◽  
B Cell Receptor ◽  
B Cell Activation ◽  
Bcr Signaling

ABSTRACTB lymphocytes form a central part of the adaptive immune system, helping to clear infections by mounting antibody responses and immunological memory. B cell activation is critically controlled by a specific antigen receptor, the B cell receptor (BCR), which triggers a complex, multibranched signaling cascade initiating various cellular changes. While parts of these pathways are reasonably well characterized, we still lack a comprehensive protein-level view of the very dynamic and robust cellular response triggered by antigen engagement. Ability to track, with sufficient kinetic resolution, the protein machineries responding to BCR signaling is imperative to provide new understanding into this complex cell activation event. We address this challenge by using APEX2 proximity labeling technique, that allows capture a major fraction of proteins in a given location with 20nm range and 1min time window, and target the APEX2 enzyme to the plasma membrane lipid raft domain, where BCR efficiently translocates upon activation. Our data provides unprecedented insights into the protein composition of lipid raft environment in B cells, and the changes triggered there upon BCR cross-linking and translocation. In total, we identified 1677 proteins locating at the vicinity of lipid raft domains in cultured mouse B cells. The data includes a majority of proteins known to be involved in proximal BCR signaling. Interestingly, our differential enrichment analysis identified various proteins that underwent dynamic changes in their localization but that had no previously known linkage to early B cell activation. As expected, we also identified, for example, a wealth of proteins linked to clathrin-mediated endocytosis that were recruited to the lipid rafts upon cell activation. We believe that his data serves as a valuable record of proteins involved in BCR activation response and aid various future studies in the field.

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