scholarly journals Missing Links in Antibody Assembly Control

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Tiziana Anelli ◽  
Eelco van Anken
Keyword(s):  
Immune Response ◽  
B Cell ◽  
B Lymphocytes ◽  
Humoral Immune Response ◽  
Disulfide Bonds ◽  
Cell Receptor ◽  
Immunoglobulin M ◽  
Dependent Manner ◽  
Humoral Immune ◽  
Secretory Igm

Fidelity of the humoral immune response requires that quiescent B lymphocytes display membrane bound immunoglobulin M (IgM) on B lymphocytes surface as part of the B cell receptor, whose function is to recognize an antigen. At the same time B lymphocytes should not secrete IgM until recognition of the antigen has occurred. The heavy chains of the secretory IgM have a C-terminal tail with a cysteine instead of a membrane anchor, which serves to covalently link the IgM subunits by disulfide bonds to form “pentamers” or “hexamers.” By virtue of the same cysteine, unassembled secretory IgM subunits are recognized and retained (via mixed disulfide bonds) by members of the protein disulfide isomerase family, in particular ERp44. This so-called “thiol-mediated retention” bars assembly intermediates from prematurely leaving the cell and thereby exerts quality control on the humoral immune response. In this essay we discuss recent findings on how ERp44 governs such assembly control in a pH-dependent manner, shuttling between the cisGolgi and endoplasmic reticulum, and finally on how pERp1/MZB1, possibly as a co-chaperone of GRP94, may help to overrule the thiol-mediated retention in the activated B cell to give way to antibody secretion.

Tetraspanins in the humoral immune response

2011 ◽  
Vol 39 (2) ◽  
pp. 512-517 ◽  
Author(s):  
Annemiek B. van Spriel
Keyword(s):  
Immune Response ◽  
B Cell ◽  
B Lymphocytes ◽  
Humoral Immune Response ◽  
Cell Biology ◽  
Transmembrane Proteins ◽  
Receptor Activation ◽  
Ample Evidence ◽  
Humoral Immune ◽  
Mhc Molecules

The tetraspanins represent a large superfamily of four-transmembrane proteins that are expressed on all nucleated cells. Tetraspanins play a prominent role in the organization of the plasma membrane by co-ordinating the spatial localization of transmembrane proteins and signalling molecules into ‘tetraspanin microdomains’. In immune cells, tetraspanins interact with key leucocyte receptors [including MHC molecules, integrins, CD4/CD8 and the BCR (B-cell receptor) complex] and as such can modulate leucocyte receptor activation and downstream signalling pathways. There is now ample evidence that tetraspanins on B-lymphocytes are important in controlling antibody production. The tetraspanin CD81 interacts with the BCR complex and is critical for CD19 expression and IgG production, whereas the tetraspanin CD37 inhibits IgA production and is important for IgG production. By contrast, the tetraspanins CD9, Tssc6 and CD151 appear dispensable for humoral immune responses. Thus individual tetraspanin family members have specific functions in B-cell biology, which is evidenced by recent studies in tetraspanin-deficient mice and humans. The present review focuses on tetraspanins expressed by B-lymphocytes and discusses novel insights into the function of tetraspanins in the humoral immune response.

scholarly journals Plasmodium vivax Cell-Traversal Protein for Ookinetes and Sporozoites: Naturally Acquired Humoral Immune Response and B-Cell Epitope Mapping in Brazilian Amazon Inhabitants

2017 ◽  
Vol 8 ◽  
Author(s):  
Rodrigo Nunes Rodrigues-da-Silva ◽  
Isabela Ferreira Soares ◽  
Cesar Lopez-Camacho ◽  
João Hermínio Martins da Silva ◽  
Daiana de Souza Perce-da-Silva ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cell ◽  
Plasmodium Vivax ◽  
Humoral Immune Response ◽  
Epitope Mapping ◽  
Cell Epitope ◽  
Brazilian Amazon ◽  
Humoral Immune ◽  
B Cell Epitope

scholarly journals Babesia bovis RON2 contains conserved B-cell epitopes that induce an invasion-blocking humoral immune response in immunized cattle

2018 ◽  
Vol 11 (1) ◽  
Author(s):  
Mario Hidalgo-Ruiz ◽  
Carlos E. Suarez ◽  
Miguel A. Mercado-Uriostegui ◽  
Ruben Hernandez-Ortiz ◽  
Juan Alberto Ramos ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cell ◽  
Humoral Immune Response ◽  
Babesia Bovis ◽  
B Cell Epitopes ◽  
Humoral Immune

scholarly journals IVIg modulates BCR signaling through CD22 and promotes apoptosis in mature human B lymphocytes

Blood ◽  
2010 ◽  
Vol 116 (10) ◽  
pp. 1698-1704 ◽  
Author(s):  
Jean-François Séïté ◽  
Divi Cornec ◽  
Yves Renaudineau ◽  
Pierre Youinou ◽  
Rizgar A. Mageed ◽  
...  
Keyword(s):  
B Cell ◽  
B Lymphocytes ◽  
B Lymphocyte ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Time Dependent ◽  
G1 Phase ◽  
Dependent Manner ◽  
Bcr Signaling ◽  
Sustained Activation

Abstract Among various mechanisms for interactions with B cells, intravenous immunoglobulin (IVIg) may operate through the insertion of its Fc part into the Fc-γ receptor, or the binding of its sialic acid (SA)–bearing glycans to the negatively regulating CD22 lectin. It appeared that IVIg reduces B lymphocyte viability in a dose- and time-dependent manner. Furthermore, we show by confocal microscopy that SA-positive IgG, but not SA-negative IgG bind to CD22. This interaction reduces the strength of B-cell receptor–mediated signaling trough down-regulating tyrosine phosphorylation of Lyn and the B-cell linker proteins, and up-regulating phospholipase Cγ2 activation. This cascade resulted in a sustained activation of Erk 1/2 and arrest of the cell cycle at the G1 phase. These changes may be accounted for the efficacy of IVIg in autoimmune diseases.

B Cell-Related Chemokine (CXCL13) in CSF is Correlated with the Intrathecal Humoral Immune Response in Patients with Multiple Sclerosis

2020 ◽  
Vol 37 ◽  
pp. 101569
Author(s):  
Sawsan Feki ◽  
Mariem Dammak ◽  
Sabrina Mejdoub ◽  
Saba Gargouri ◽  
Salma Sakka ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
B Cell ◽  
Humoral Immune Response ◽  
Humoral Immune

Vav-2 signalling participates in the humoral immune response and B cell maturation

2001 ◽  
Vol 29 (5) ◽  
pp. A129-A129
Author(s):  
G. Doody ◽  
S. Bell ◽  
E. Vigorito ◽  
E. Clayton ◽  
S. McAdam ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cell ◽  
Humoral Immune Response ◽  
Cell Maturation ◽  
Humoral Immune ◽  
B Cell Maturation

A New Vaccine Paradigm To Break Tolerance with Potential Applications for the Immunotherapy of B Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1411-1411
Author(s):  
Ronald P. Taylor ◽  
Emily C. Whipple ◽  
Margaret A. Lindorfer ◽  
Andrew H. Ditto ◽  
Ryan S. Shanahan
Keyword(s):  
Flow Cytometry ◽  
Immune Response ◽  
B Cells ◽  
B Cell ◽  
Humoral Immune Response ◽  
Critical Role ◽  
B Cell Lymphoma ◽  
Breakdown Product ◽  
Humoral Immune ◽  
Mouse Igg2a

Abstract Complement (C) plays a critical role in the immune response by opsonizing immune complexes (IC) and thymus-independent type 2 antigens with C3 breakdown product C3dg. We investigated the in vivo fate and handling in mice of anti-CR1/CR2 mAb 7G6. We used this rat IgG mAb as a surrogate for C3dg-opsonized IC; mAb 7G6 binds to CR1/CR2 with high affinity, blocks C3dg binding and saturates mouse B cell CR2 at inputs of only 2 ug. RIA, flow cytometry, and fluorescence immunohistochemistry were used to examine the disposition of 0.5–2 ug quantities of mAb 7G6 infused i.v. in mice. The mAb binds to circulating B cells and in the spleen binds preferentially to marginal zone (MZ) B cells. However, within 24 h MZ B cells relocate and transfer the mAb to regions rich in follicular dendritic cells (FDC). Localization of intact antigen to FDC should induce a substantial immune response, and therefore we immunized mice and monkeys i.v. with low doses (1–20 ug/kg) of prototype antigens constructed with anti-CR1/2 mAb 7G6 or anti-CR2 mAb HB135, respectively. We observed a strong immune response characterized by early development of IgG antibodies and long-lasting immunity extending out to at least one year. We applied our immunization paradigm to mouse IgG idiotypes, based on i.v. infusion of mouse IgG2a mAbs which were cross-linked with mAb 7G6. The purpose of these experiments was to determine if tolerance can be broken in order to develop a more powerful vaccine strategy to induce a cytotoxic humoral immune response to malignant B cells based on targeting the idiotype of immunoglobulin molecules expressed on their surfaces. I.V. immunization with the constructs indeed generated a mouse IgG1 immune response to two different mouse IgG2a mAbs, as demonstrated by ELISA. The immune response was idiotype specific, but some anti-isotype antibodies were also detected. Moreover, sera from immunized mice immunoprecipitated the specific radiolabeled mouse mAbs in the presence of 7.5% polyethylene glycol. This humoral immune response was also demonstrable in flow cytometry assays in which IgG1 in sera of immunized mice bound to erythrocytes opsonized with bispecific mAb constructs consisting of the IgG2a mAb crosslinked with an anti-CR1 mAb. The present approach, based on coupling the targeted immunoglobulin to an anti-CR2 mAb for delivery to FDC, may lead to a more effective immunotherapeutic vaccine compared to methods currently in clinical trials which require use of glutaraldehyde to effect crosslinking of the targeted immunoglobulin to KLH.

Sign in / Sign up

Export Citation Format

Share Document