scholarly journals The immunosenescence-related factor DOCK11 is involved in secondary immune responses of B cells

2022 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuma Sugiyama ◽  
Mitsuhiro Fujiwara ◽  
Akihiko Sakamoto ◽  
Hiromichi Tsushima ◽  
Akihiko Nishikimi ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
Germinal Center ◽  
Protein Antigen ◽  
Related Factor ◽  
Limited Information ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
T Cell Help

Abstract Background Memory B cells are an antigen-experienced B-cell population with the ability to rapidly differentiate into antibody-producing cells by recall responses. We recently found that dedicator of cytokinesis 11 (DOCK11) contributes to the expansion of antigen-specific populations among germinal center B cells upon immunization. In comparison, limited information is available on the contribution of DOCK11 to secondary humoral immune responses. Results In this study, effects of the DOCK11 deficiency in B cells were examined on secondary immune responses to protein antigen. The lack of DOCK11 in B cells resulted in the impaired induction of antibody-producing cells upon secondary immunization with protein antigen. DOCK11 was dispensable for the recall responses of antigen-experienced B cells, as demonstrated by the comparable induction of antibody-producing cells in mice given transfer of antigen-experienced B cells with no DOCK11 expression. Instead, the lack of DOCK11 in B cells resulted in the impaired secondary immune responses in a B cell-extrinsic manner, which was recovered by the adoptive transfer of cognate T cells. Conclusions We addressed that intrinsic and extrinsic effects of DOCK11 expression in B cells may contribute to secondary humoral immune responses in manner of the induction of cognate T-cell help.

scholarly journals Recombinant Rabies Virus Overexpressing OX40-Ligand Enhances Humoral Immune Responses by Increasing T Follicular Helper Cells and Germinal Center B Cells

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 144 ◽  
Author(s):  
Yingying Li ◽  
Ling Zhao ◽  
Baokui Sui ◽  
Zhaochen Luo ◽  
Yachun Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Immune Responses ◽  
Rabies Virus ◽  
Germinal Center ◽  
Rabies Vaccine ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Follicular Helper ◽  
Ox40 Ligand

Rabies, caused by the rabies virus (RABV), remains a serious threat to public health in most countries. Development of a single-dose and efficacious rabies vaccine is the most important method to restrict rabies virus transmission. Costimulatory factor OX40-ligand (OX40L) plays a crucial role in the T cell-dependent humoral immune responses through T-B cell interaction. In this work, a recombinant RABV overexpressing mouse OX40L (LBNSE-OX40L) was constructed, and its effects on immunogenicity were evaluated in a mouse model. LBNSE-OX40L-immunized mice generated a larger number of T follicular helper (Tfh) cells, germinal center (GC) B cells, and plasma cells (PCs) than the parent virus LBNSE-immunized mice. Furthermore, LBNSE-OX40L induced significantly higher levels of virus-neutralizing antibodies (VNA) as early as seven days post immunization (dpi), which lasted for eight weeks, resulting in better protection for mice than LBNSE (a live-attenuated rabies vaccine strain). Taken together, our data in this study suggest that OX40L can be a novel and potential adjuvant to improve the induction of protective antibody responses post RABV immunization by triggering T cell-dependent humoral immune responses, and that LBNSE-OX40L can be developed as an efficacious and nonpathogenic vaccine for animals.

scholarly journals Essential role of immobilized chemokine CXCL12 in the regulation of the humoral immune response

2017 ◽  
Vol 114 (9) ◽  
pp. 2319-2324 ◽  
Author(s):  
Aleksandr Barinov ◽  
Lingjie Luo ◽  
Pamela Gasse ◽  
Vannary Meas-Yedid ◽  
Emmanuel Donnadieu ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
Germinal Center ◽  
Affinity Maturation ◽  
Humoral Immune ◽  
Germinal Center Reaction ◽  
Humoral Immune Responses ◽  
Binding Domains ◽  
Chemokine Cxcl12

Chemokines control the migration of a large array of cells by binding to specific receptors on cell surfaces. The biological function of chemokines also depends on interactions between nonreceptor binding domains and proteoglycans, which mediate chemokine immobilization on cellular or extracellular surfaces and formation of fixed gradients. Chemokine gradients regulate synchronous cell motility and integrin-dependent cell adhesion. Of the various chemokines, CXCL12 has a unique structure because its receptor-binding domain is distinct and does not overlap with the immobilization domains. Although CXCL12 is known to be essential for the germinal center (GC) response, the role of its immobilization in biological functions has never been addressed. In this work, we investigated the unexplored paradigm of CXCL12 immobilization during the germinal center reaction, a fundamental process where cellular traffic is crucial for the quality of humoral immune responses. We show that the structure of murine germinal centers and the localization of GC B cells are impaired when CXCL12 is unable to bind to cellular or extracellular surfaces. In such mice, B cells carry fewer somatic mutations in Ig genes and are impaired in affinity maturation. Therefore, immobilization of CXCL12 is necessary for proper trafficking of B cells during GC reaction and for optimal humoral immune responses.

scholarly journals Impaired Immune Responses and B-Cell Proliferation in Mice Lacking the Id3 Gene

1999 ◽  
Vol 19 (9) ◽  
pp. 5969-5980 ◽  
Author(s):  
Lihua Pan ◽  
Shinichi Sato ◽  
Joshua P. Frederick ◽  
Xiao-Hong Sun ◽  
Yuan Zhuang
Keyword(s):  
Cell Cycle ◽  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
Cell Cycle Progression ◽  
Cross Linking ◽  
Cycle Progression ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Deficient Mice

ABSTRACT B-lymphocyte activation and proliferation induced by the B-cell receptor (BCR) signals are important steps in the initiation of humoral immune responses. How the BCR signals are translated by nuclear transcription factors into cell cycle progression is poorly understood.Id3 is an immediate-early gene responding to growth and mitogenic signals in many cell types including B cells. The primary function of the Id3 protein has been defined as that of inhibitor of basic-helix-loop-helix (bHLH) transcription factors. The interaction between Id3 and bHLH proteins, many of which are essential for cellular differentiation, has been proposed as a key regulatory event leading to cellular proliferation instead of differentiation. To further investigate the role of Id3 in tissue and embryo development and the mechanism of Id3-mediated growth regulation, we generated and analyzedId3-deficient mice. While these mice display no overt abnormality in tissue and embryo development, their humoral immunity is compromised. The amounts of immunoglobulins produced inId3-deficient mice immunized with a T-cell-dependent antigen and a type 2 T-cell-independent antigen are attenuated and severely impaired, respectively. Further analysis of lymphocytes isolated from Id3-deficient mice reveals a B-cell defect in their proliferation response to BCR cross-linking but not to lipopolysaccharide or a combination of BCR cross-linking and interleukin-4. Analyses of cultured lymphocytes also suggest involvement of Id3 in cytokine production in T cells and isotype switching in B cells. Finally, the proliferation defect inId3-deficient B cells can be rescued by ectopic expression of Id1, a homologue of Id3. Taken together, these results define a necessary and specific role for Id3 in mediating signals from BCR to cell cycle progression during humoral immune responses.

scholarly journals Requirement for CD1d expression by B cells to stimulate NKT cell–enhanced antibody production

Blood ◽  
2008 ◽  
Vol 111 (4) ◽  
pp. 2158-2162 ◽  
Author(s):  
Gillian A. Lang ◽  
T. Scott Devera ◽  
Mark L. Lang
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
Antibody Production ◽  
Nkt Cells ◽  
Nkt Cell ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Cell Expression ◽  
Antigen Presenting

Activation of natural killer-like T (NKT) cells with the CD1d ligand α-galactosylceramide enhances T-dependent humoral immune responses against coadministered T-dependent Ag. At present, there is little information on the mechanisms involved other than a dependence on CD1d expression by antigen-presenting cells and/or development of the NKT subset. We therefore tested the hypothesis that direct presentation of α-GC by B cells was required for NKT-enhanced Ab responses against T-dependent Ag. We reconstituted B cell–deficient μMT mice with B cells from C57Bl/6 donors or CD1d−/− donors before immunization with NP-KLH alone or NP-KLH mixed with α-GC. We made the surprising observation that B-cell expression of CD1d is absolutely required for the NKT-enhanced Ab response. Our data show that the mechanism by which NKT cells enhance humoral immune responses involves interaction with CD1d-expressing B cells.

scholarly journals Methamphetamine Compromises the Adaptive B Cell-Mediated Immunity to Antigenic Challenge in C57BL/6 Mice

2021 ◽  
Vol 3 ◽  
Author(s):  
Anum N. Mitha ◽  
Daniela Chow ◽  
Valerie Vaval ◽  
Paulina Guerrero ◽  
Dormarie E. Rivera-Rodriguez ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Adaptive Immunity ◽  
Humoral Immunity ◽  
Cell Mediated Immunity ◽  
Limited Information ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
The Impact

Methamphetamine (METH) is a substance of abuse that causes dysregulation of the innate and adaptive immunity in users. B cells are involved in the humoral component of the adaptive immunity by producing and secreting antibodies (Abs). METH modifies Ab production, although limited information on the impact of this psychostimulant on antigen (Ag)-specific humoral immune responses is available. Since T cell-dependent and T cell-independent Ags are involved in the activation of B lymphocytes, we explored the role of METH on humoral immunity to ovalbumin (OVA; T cell-dependent) and bacterial lipopolysaccharide (LPS; T cell-independent) in C57BL/6 mice. We demonstrated that METH extends the infiltration of B cells into pulmonary and splenic tissues 7 days post-Ag challenge. METH impairs Ab responses in the blood of animals challenged with OVA and LPS. Furthermore, METH diminishes the expression and distribution of IgM on B cell surface, suggesting a possible detrimental impact on users' humoral immunity to infection or autoimmunity.

scholarly journals Critical role of the IgM Fc receptor in IgM homeostasis, B-cell survival, and humoral immune responses

2012 ◽  
Vol 109 (40) ◽  
pp. E2699-E2706 ◽  
Author(s):  
R. Ouchida ◽  
H. Mori ◽  
K. Hase ◽  
H. Takatsu ◽  
T. Kurosaki ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Cell Survival ◽  
Critical Role ◽  
Fc Receptor ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
B Cell Survival

scholarly journals Germinal center B cell development has distinctly regulated stages completed by disengagement from T cell help

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Ting-ting Zhang ◽  
David G Gonzalez ◽  
Christine M Cote ◽  
Steven M Kerfoot ◽  
Shaoli Deng ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
B Cell Differentiation ◽  
B Cell Maturation ◽  
Germinal Center B Cell ◽  
T Cell Help ◽  
Dose Dependent

To reconcile conflicting reports on the role of CD40 signaling in germinal center (GC) formation, we examined the earliest stages of murine GC B cell differentiation. Peri-follicular GC precursors first expressed intermediate levels of BCL6 while co-expressing the transcription factors RelB and IRF4, the latter known to repress Bcl6 transcription. Transition of GC precursors to the BCL6hi follicular state was associated with cell division, although the number of required cell divisions was immunogen dose dependent. Potentiating T cell help or CD40 signaling in these GC precursors actively repressed GC B cell maturation and diverted their fate towards plasmablast differentiation, whereas depletion of CD4+ T cells promoted this initial transition. Thus while CD40 signaling in B cells is necessary to generate the immediate precursors of GC B cells, transition to the BCL6hi follicular state is promoted by a regional and transient diminution of T cell help.

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