scholarly journals The mechanism of humoral immune response to allogeneic organ transplantation

2017 ◽  
Vol 19 (2) ◽  
pp. 139-151
Author(s):  
A. S. Berkos ◽  
G. V. Nikolaev
Keyword(s):  
B Cell ◽  
Hla Antigens ◽  
Cross Reactivity ◽  
Affinity Maturation ◽  
Donor Organ ◽  
Humoral Immune ◽  
Antibody Mediated Rejection ◽  
Human Leucocyte Antigens ◽  
Hla Compatibility ◽  
Leucocyte Antigens

The problem of antibody-mediated rejection of donor organ remains extremely relevant. The main targets of the antibodies are mainly donor HLA-antigens (Human Leucocyte Antigens), expressed, in particular, by the cells of graft vascular endothelium. This review describes the mechanisms of the development of humoral alloimmunity which are based on B-cell recognition of epitopes of donor HLA-molecules and affinity maturation of B-cell receptors in the germinal centers of peripheral lymphatic system. Monitoring of epitope load and cross-reactivity indicators to evaluate HLA-compatibility of donor and recipient plays an important role in the prevention of allograft humoral rejection.

scholarly journals The in vivo function of a noncanonical TRAF2-binding domain in the C-terminus of CD40 in driving B-cell growth and differentiation

Blood ◽  
2007 ◽  
Vol 110 (1) ◽  
pp. 193-200 ◽  
Author(s):  
Li-Fan Lu ◽  
Cory L. Ahonen ◽  
Evan F. Lind ◽  
Vanitha S. Raman ◽  
W. James Cook ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Cell Activation ◽  
Affinity Maturation ◽  
Functional Domain ◽  
Antibody Isotype ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Cell Immunity

The recruitment of tumor necrosis factor receptor–associated factors (TRAFs) 1, 2, 3, 5, and 6 to the CD40 cytoplasmic tail upon CD40 trimerization results in downstream signaling events that ultimately lead to CD40-dependent, thymus-dependent (TD) humoral immune responses. Previously, we have shown signaling through the C-terminal tail of CD40 in the absence of canonical TRAF-binding sites is capable of signaling through an alternative TRAF2-binding site. Here, we demonstrate that B cells from mice harboring CD40 with only the C-terminal tail can activate both canonical and noncanonical NFκB signaling pathways. Moreover, while lacking germinal center formation, several hallmarks of humoral immune responses including clonal B-cell activation/expansion, antibody isotype switching, and affinity maturation remain normal. This study demonstrates a new functional domain in CD40 that controls critical aspects of B-cell immunity in an in vivo setting.

scholarly journals Sustained antibody response to ZIKV infection induced by NS1 protein is accompanied by the progressive appearance of autoreactive antibodies and cross-reactive B cell clones

2020 ◽  
Author(s):  
Cecilia B. Cavazzoni ◽  
Vicente B. T. Bozza ◽  
Lucas Tostes ◽  
Bruno Maia ◽  
Luka Mesin ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cell ◽  
Humoral Immune Response ◽  
Zika Virus ◽  
Cross Reactivity ◽  
Ns1 Protein ◽  
Structural Protein ◽  
Humoral Immune ◽  
Autoreactive Antibodies ◽  
Cell Clones

AbstractAntibodies are key players in controlling viral infections. However, in addition to antigen-specific responses to viral antigens, humoral immune response can generate polyreactive and autoreactive antibodies of unknown function. Dengue and Zika virus infections have been linked to autoimmune disorders including Guillain-Barrè syndrome. A unique feature of flaviviruses is the secretion of non-structural protein 1 (NS1) by infected cells. NS1 is highly immunogenic and antibodies targeting NS1 can have both protective and pathogenic roles. In the present study, we investigated the humoral immune response to Zika virus NS1 and found NS1 to be an immunodominant viral antigen correlated to the presence of autoreactive antibodies. Through single B cell cultures, we coupled binding assays and BCR sequencing, confirming the immunodominance of NS1 and the presence of self-reactive clones in germinal centers both after infection and immunization, some of which were cross-reactivity with NS1. Anti-NS1 B cell clones showed features related to pathogenic autoreactive antibodies. Our findings demonstrate NS1 immunodominance at the cellular level as well as a potential role for NS1 in ZIKV associated autoimmune manifestations.

scholarly journals Shared B cell memory to coronaviruses and other pathogens varies in human age groups and tissues

Science ◽  
2021 ◽  
pp. eabf6648
Author(s):  
Fan Yang ◽  
Sandra C. A. Nielsen ◽  
Ramona A. Hoh ◽  
Katharina Röltgen ◽  
Oliver Fabian Wirz ◽  
...  
Keyword(s):  
B Cell ◽  
Clonal Evolution ◽  
Age Groups ◽  
Organ Donor ◽  
Cross Reactivity ◽  
Immune Memory ◽  
Lymphoid Tissues ◽  
Cell Memory ◽  
Humoral Immune ◽  
B Cell Memory

Vaccination and infection promote the formation, tissue distribution, and clonal evolution of B cells, which encode humoral immune memory. We evaluated convergent antigen-specific antibody genes of similar sequences shared between individuals in pediatric and adult blood, and deceased organ donor tissues. B cell memory varied for different pathogens. Polysaccharide antigen-specific clones were not exclusive to the spleen. Adults had higher clone frequencies and greater class-switching in lymphoid tissues than blood, while pediatric blood had abundant class-switched convergent clones. Consistent with reported serology, pre-pandemic children had class-switched convergent clones to SARS-CoV-2 with weak cross-reactivity to other coronaviruses, while adult blood or tissues showed few such clones. The results highlight the prominence of early childhood B cell clonal expansions and cross-reactivity for future responses to novel pathogens.

scholarly journals The immunodominant antibody response to Zika virus NS1 protein is characterized by cross-reactivity to self

2021 ◽  
Vol 218 (9) ◽  
Author(s):  
Cecilia B. Cavazzoni ◽  
Vicente B.T. Bozza ◽  
Tostes C.V. Lucas ◽  
Luciana Conde ◽  
Bruno Maia ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cell ◽  
Humoral Immune Response ◽  
Zika Virus ◽  
Nonstructural Protein ◽  
Cross Reactivity ◽  
Ns1 Protein ◽  
Humoral Immune ◽  
Nonstructural Protein 1 ◽  
Autoreactive Antibodies

Besides antigen-specific responses to viral antigens, humoral immune response in virus infection can generate polyreactive and autoreactive antibodies. Dengue and Zika virus infections have been linked to antibody-mediated autoimmune disorders, including Guillain-Barré syndrome. A unique feature of flaviviruses is the secretion of nonstructural protein 1 (NS1) by infected cells. NS1 is highly immunogenic, and antibodies targeting NS1 can have both protective and pathogenic roles. In the present study, we investigated the humoral immune response to Zika virus NS1 and found NS1 to be an immunodominant viral antigen associated with the presence of autoreactive antibodies. Through single B cell cultures, we coupled binding assays and BCR sequencing, confirming the immunodominance of NS1. We demonstrate the presence of self-reactive clones in germinal centers after both infection and immunization, some of which present cross-reactivity with NS1. Sequence analysis of anti-NS1 B cell clones showed sequence features associated with pathogenic autoreactive antibodies. Our findings demonstrate NS1 immunodominance at the cellular level as well as a potential role for NS1 in ZIKV-associated autoimmune manifestations.

scholarly journals The concerted change in the distribution of cell cycle phases and zone composition in germinal centers is regulated by IL-21

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dimitra Zotos ◽  
Isaak Quast ◽  
Connie S. N. Li-Wai-Suen ◽  
Craig I. McKenzie ◽  
Marcus J. Robinson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
B Cells ◽  
B Cell ◽  
Cell Cycle Progression ◽  
Affinity Maturation ◽  
Antibody Affinity ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Important Regulator

AbstractHumoral immune responses require germinal centres (GC) for antibody affinity maturation. Within GC, B cell proliferation and mutation are segregated from affinity-based positive selection in the dark zone (DZ) and light zone (LZ) substructures, respectively. While IL-21 is known to be important in affinity maturation and GC maintenance, here we show it is required for both establishing normal zone representation and preventing the accumulation of cells in the G1 cell cycle stage in the GC LZ. Cell cycle progression of DZ B cells is unaffected by IL-21 availability, as is the zone phenotype of the most highly proliferative GC B cells. Collectively, this study characterises the development of GC zones as a function of time and B cell proliferation and identifies IL-21 as an important regulator of these processes. These data help explain the requirement for IL-21 in normal antibody affinity maturation.

scholarly journals Hide and seek: interplay between influenza viruses and B cells

2020 ◽  
Vol 32 (9) ◽  
pp. 605-611 ◽  
Author(s):  
Masayuki Kuraoka ◽  
Yu Adachi ◽  
Yoshimasa Takahashi
Keyword(s):  
B Cells ◽  
B Cell ◽  
Surface Protein ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Native Structure ◽  
Humoral Immune ◽  
Protective Antibodies ◽  
Major Surface ◽  
And Function

Abstract Influenza virus constantly acquires genetic mutations/reassortment in the major surface protein, hemagglutinin (HA), resulting in the generation of strains with antigenic variations. There are, however, HA epitopes that are conserved across influenza viruses and are targeted by broadly protective antibodies. A goal for the next-generation influenza vaccines is to stimulate B-cell responses against such conserved epitopes in order to provide broad protection against divergent influenza viruses. Broadly protective B cells, however, are not easily activated by HA antigens with native structure, because the virus has multiple strategies to escape from the humoral immune responses directed to the conserved epitopes. One such strategy is to hide the conserved epitopes from the B-cell surveillance by steric hindrance. Technical advancement in the analysis of the human B-cell antigen receptor (BCR) repertoire has dissected the BCRs to HA epitopes that are hidden in the native structure but are targeted by broadly protective antibodies. We describe here the characterization and function of broadly protective antibodies and strategies that enable B cells to seek these hidden epitopes, with potential implications for the development of universal influenza vaccines.

scholarly journals B-cell activating factor BAFF as a novel alert marker for the immunological risk stratification after kidney transplantation

2021 ◽  
Author(s):  
Antonia Margarete Schuster ◽  
N. Miesgang ◽  
L. Steines ◽  
C. Bach ◽  
B. Banas ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
B Cell ◽  
Graft Function ◽  
Risk Profile ◽  
Kidney Transplant Recipients ◽  
Post Transplantation ◽  
Antibody Mediated Rejection ◽  
B Cell Activating Factor ◽  
Medium Risk ◽  
Patients At Risk

AbstractThe B cell activating factor BAFF has gained importance in the context of kidney transplantation due to its role in B cell survival. Studies have shown that BAFF correlates with an increased incidence of antibody-mediated rejection and the development of donor-specific antibodies. In this study, we analyzed a defined cohort of kidney transplant recipients who were treated with standardized immunosuppressive regimens according to their immunological risk profile. The aim was to add BAFF as an awareness marker in the course after transplantation to consider patient’s individual immunological risk profile. Included patients were transplanted between 2016 and 2018. Baseline data, graft function, the occurrence of rejection episodes, signs of microvascular infiltration, and DSA kinetics were recorded over 3 years. BAFF levels were determined 14 d, 3 and 12 months post transplantation. Although no difference in graft function could be observed, medium-risk patients showed a clear dynamic in their BAFF levels with low levels shortly after transplantation and an increase in values of 123% over the course of 1 year. Patients with high BAFF values were more susceptible to rejection, especially antibody-mediated rejection and displayed intensified microvascular inflammation; the combination of high BAFF + DSA puts patients at risk. The changing BAFF kinetics of the medium risk group as well as the increased occurrence of rejections at high BAFF values enables BAFF to be seen as an awareness factor. To compensate the changing immunological risk, a switch from a weaker induction therapy to an intensified maintenance therapy is required.

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
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