scholarly journals A Novel Image Analysis Approach Reveals a Role for Complement Receptors 1 and 2 in Follicular Dendritic Cell Organization in Germinal Centers

2021 ◽  
Vol 12 ◽  
Author(s):  
Jessica C. Anania ◽  
Annika Westin ◽  
Jeremy Adler ◽  
Birgitta Heyman
Keyword(s):  
B Cells ◽  
Follicular Dendritic Cell ◽  
Cell Interaction ◽  
Germinal Centers ◽  
Affinity Maturation ◽  
Receptor Expression ◽  
Complement Receptors ◽  
Serum Samples ◽  
Knock Out ◽  
Follicular Dendritic

Follicular dendritic cells (FDCs) are rare and enigmatic cells that mainly reside in germinal centers (GCs). They are capable of capturing immune complexes, via their Fc (FcRs) and complement receptors (CRs) and storing them for long periods in non-degradative vesicles. Presentation of ICs on FDCs to B cells is believed to drive affinity maturation. CR1 and CR2 are expressed on B cells and FDCs. Cr2 knock out (KO) mice, lacking both receptors, have impaired antibody and GC responses. Utilizing a novel ImageJ macro to analyze confocal fluorescence microscopy images of spleen sections, we here investigate how FDCs in wild type (WT) and Cr2 KO mice behave during the first two weeks after immunization with sheep red blood cells (SRBC). Mice were immunized with SRBC i.v. and spleen and serum samples harvested at various time points. As expected, antibody and GC responses in Cr2 KO mice were impaired in comparison to WT mice. Fewer FDCs were identified in Cr2 KO mice, and these exhibited differential localization and organization in comparison to WT mice. WT FDCs were primarily located within GCs at the light zone/dark zone border. FDCs from WT but not Cr2 KO mice were actively dispersed in GCs, i.e. tended to move away from each other, presumably to increase their surface area for B cell interaction. FDCs from Cr2 KO mice were more often found on follicles outside of the GCs and those within the GCs were closer to the periphery in comparison to WT FDCs. Expression of CR1 and CR2, FcγRIIB, and FcµR increased in FDCs from WT mice during the course of immunization. The results suggest that decreased ability to capture ICs by FDCs lacking CR1 and CR2 may not be the only explanation for the impaired GC and antibody responses in Cr2 KO mice. Poor FDC organization in GCs and failure to increase receptor expression after immunization may further contribute to the inefficient immune responses observed.

scholarly journals Enhanced Follicular Dendritic Cell-B Cell Interaction in HIV and SIV Infections and its Potential Role in Polyclonal B Cell Activation

1998 ◽  
Vol 6 (1-2) ◽  
pp. 61-70 ◽  
Author(s):  
Yvonne J. Rosenberg ◽  
Mark. G. Lewis ◽  
Marie H. Kosco-Vilbois
Keyword(s):  
Lymph Node ◽  
Dendritic Cell ◽  
B Cell ◽  
Cell Activation ◽  
Follicular Dendritic Cell ◽  
Cell Interaction ◽  
Germinal Centers ◽  
B Cell Activation ◽  
Immunodeficiency Virus ◽  
Follicular Dendritic

Human immunodeficiency virus (HIV) infections have been characterized by both polyclonal Bcell activation and enhanced responsiveness to B-cell growth factors on one hand and the loss of specific antibody (Ab) responses and refractoriness to the normal signals for B-cell activation on the other. Histopathological studies of lymph node from HIV- and simian immunodeficiency virus (SIV)-infected individuals have indicated initial follicular hyperplasia and the appearance of large irregular germinal centers that undergo progressive involution concomitant with follicular dendritic-cell (FDC) disruption. During this process, follicular dendritic-cell -enriched lymph-node-cell cultures exhibit increased ability to induce cluster formation (“in vitrogerminal centers”), lymphocyte proliferation and antibody production compared to uninfected controls. This paper discusses how enhanced FDC-B-cell interaction within SIV-infected germinal centers may result in a reduced ability to select high-affinity B cells and alter the dynamics of antibodyproducing- cell and memory-cell generation resulting in the observed hyperactivity.

scholarly journals Lymph Node Germinal Centers Form in the Absence of Follicular Dendritic Cell Networks

1999 ◽  
Vol 189 (5) ◽  
pp. 855-864 ◽  
Author(s):  
Pandelakis A. Koni ◽  
Richard A. Flavell
Keyword(s):  
Dendritic Cell ◽  
B Cell ◽  
Follicular Dendritic Cell ◽  
Germinal Centers ◽  
Affinity Maturation ◽  
Antibody Affinity ◽  
B Cell Memory ◽  
Follicular Dendritic ◽  
Cell Networks ◽  
Deficient Mice

Follicular dendritic cell networks are said to be pivotal to both the formation of germinal centers (GCs) and their functions in generating antigen-specific antibody affinity maturation and B cell memory. We report that lymphotoxin β–deficient mice form GC cell clusters in the gross anatomical location expected of GCs, despite the complete absence of follicular dendritic cell networks. Furthermore, antigen-specific GC generation was at first relatively normal, but these GCs then rapidly regressed and GC-phase antibody affinity maturation was reduced. Lymphotoxin β–deficient mice also showed substantial B cell memory in their mesenteric lymph nodes. This memory antibody response was of relatively low affinity for antigen at week 4 after challenge, but by week 10 after challenge was comparable to wild-type, indicating that affinity maturation had failed in the GC phase but developed later.

scholarly journals Censoring of Self-Reactive B Cells by Follicular Dendritic Cell–Displayed Self-Antigen

2013 ◽  
Vol 191 (3) ◽  
pp. 1082-1090 ◽  
Author(s):  
Irene W. Yau ◽  
Matthew H. Cato ◽  
Julia Jellusova ◽  
Tatiana Hurtado de Mendoza ◽  
Robert Brink ◽  
...  
Keyword(s):  
B Cells ◽  
Dendritic Cell ◽  
Follicular Dendritic Cell ◽  
Follicular Dendritic ◽  
Self Antigen

scholarly journals Cbl and Cbl-b control the germinal center reaction by facilitating naive B cell antigen processing

2020 ◽  
Vol 217 (9) ◽  
Author(s):  
Xin Li ◽  
Liying Gong ◽  
Alexandre P. Meli ◽  
Danielle Karo-Atar ◽  
Weili Sun ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
Antigen Processing ◽  
Cell Interaction ◽  
Affinity Maturation ◽  
Antigen Uptake ◽  
Cell Antigen ◽  
Germinal Center Reaction ◽  
Follicular Helper

Antigen uptake and presentation by naive and germinal center (GC) B cells are different, with the former expressing even low-affinity BCRs efficiently capture and present sufficient antigen to T cells, whereas the latter do so more efficiently after acquiring high-affinity BCRs. We show here that antigen uptake and processing by naive but not GC B cells depend on Cbl and Cbl-b (Cbls), which consequently control naive B and cognate T follicular helper (Tfh) cell interaction and initiation of the GC reaction. Cbls mediate CD79A and CD79B ubiquitination, which is required for BCR-mediated antigen endocytosis and postendocytic sorting to lysosomes, respectively. Blockade of CD79A or CD79B ubiquitination or Cbls ligase activity is sufficient to impede BCR-mediated antigen processing and GC development. Thus, Cbls act at the entry checkpoint of the GC reaction by promoting naive B cell antigen presentation. This regulation may facilitate recruitment of naive B cells with a low-affinity BCR into GCs to initiate the process of affinity maturation.

scholarly journals The G protein–coupled receptor P2RY8 and follicular dendritic cells promote germinal center confinement of B cells, whereas S1PR3 can contribute to their dissemination

2015 ◽  
Vol 212 (13) ◽  
pp. 2213-2222 ◽  
Author(s):  
Jagan R. Muppidi ◽  
Erick Lu ◽  
Jason G. Cyster
Keyword(s):  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
Follicular Dendritic Cell ◽  
Dependent Manner ◽  
Downstream Effector ◽  
Cell Clustering ◽  
Cell Association ◽  
Sphingosine 1 Phosphate ◽  
Follicular Dendritic

The orphan Gα13-coupled receptor P2RY8 is mutated in human germinal center (GC)–derived lymphomas and was recently found to promote B cell association with GCs in a mouse model. Here we establish that P2RY8 promotes clustering of activated B cells within follicles in a follicular dendritic cell (FDC)–dependent manner. Although mice lack a P2RY8 orthologue, we show that mouse GC B cell clustering is also dependent on FDCs acting to support the function of a Gα13-coupled receptor. Mutations in GNA13 and its downstream effector ARHGEF1 are associated with the development of disseminated GC-derived lymphomas. We find that egress of Gna13 mutant GC B cells from lymph nodes in the mouse depends on sphingosine-1-phosphate receptor-3. These findings provide evidence that FDCs promote GC confinement of both human and mouse GC B cells via Gα13-dependent pathways, and they show that dissemination of Gα13-deficient GC B cells additionally requires an egress-promoting receptor.

scholarly journals B Lymphocytes Induce the Formation of Follicular Dendritic Cell Clusters in a Lymphotoxin α–dependent Fashion

1998 ◽  
Vol 187 (7) ◽  
pp. 1009-1018 ◽  
Author(s):  
Yang-Xin Fu ◽  
Guangming Huang ◽  
Yang Wang ◽  
David D. Chaplin
Keyword(s):  
T Cells ◽  
B Cells ◽  
Dendritic Cell ◽  
Follicular Dendritic Cell ◽  
Lymphoid Tissues ◽  
Immune Functions ◽  
Activated T Cells ◽  
Humoral Immune ◽  
Follicular Dendritic

Lymphotoxin (LT)α is expressed by activated T cells, especially CD4+ T helper type 1 cells, and by activated B and natural killer cells, but the functions of this molecule in vivo are incompletely defined. We have previously shown that follicular dendritic cell (FDC) clusters and germinal centers (GCs) are absent from the peripheral lymphoid tissues of LTα-deficient (LTα−/−) mice. LTα−/− mice produce high levels of antigen-specific immunoglobulin (Ig)M, but very low levels of IgG after immunization with sheep red blood cells. We show here that LTα-expressing B cells are essential for the recovery of primary, secondary, and memory humoral immune responses in LTα−/− mice. It is not necessary for T cells to express LTα to support these immune functions. Importantly, LTα-expressing B cells alone are essential and sufficient for the formation of FDC clusters. Once these clusters are formed by LTα-expressing B cells, then LTα-deficient T cells can interact with B cells to generate GCs and productive class-switched antibody responses. Thus, B cells themselves provide an essential signal that induces and maintains the lymphoid microenvironment essential for GC formation and class-switched Ig responses.

The immunoglobulin heavy-chain locus hs3b and hs4 3′ enhancers are dispensable for VDJ assembly and somatic hypermutation

Blood ◽  
2003 ◽  
Vol 102 (4) ◽  
pp. 1421-1427 ◽  
Author(s):  
Caroline Le Morvan ◽  
Eric Pinaud ◽  
Catherine Decourt ◽  
Armelle Cuvillier ◽  
Michel Cogné
Keyword(s):  
B Cells ◽  
B Cell ◽  
Heavy Chain ◽  
Somatic Hypermutation ◽  
Class Switch Recombination ◽  
Immunoglobulin Heavy Chain ◽  
Germinal Centers ◽  
Affinity Maturation ◽  
Class Switch ◽  
Endogenous Locus

Abstract The more distal enhancers of the immunoglobulin heavy-chain 3′ regulatory region, hs3b and hs4, were recently demonstrated as master control elements of germline transcription and class switch recombination to most immunoglobulin constant genes. In addition, they were shown to enhance the accumulation of somatic mutations on linked transgenes. Since somatic hypermutation and class switch recombination are tightly linked processes, their common dependency on the endogenous locus 3′ enhancers could be an attractive hypothesis. VDJ structure and somatic hypermutation were analyzed in B cells from mice carrying either a heterozygous or a homozygous deletion of these enhancers. We find that hs3b and hs4 are dispensable both for VDJ assembly and for the occurrence of mutations at a physiologic frequency in the endogenous locus. In addition, we show that cells functionally expressing the immunoglobulin M (IgM) class B-cell receptor encoded by an hs3b/hs4-deficient locus were fully able to enter germinal centers, undergo affinity maturation, and yield specific antibody responses in homozygous mutant mice, where IgG1 antibodies compensated for the defect in other IgG isotypes. By contrast, analysis of Peyer patches from heterozygous animals showed that peanut agglutinin (PNAhigh) B cells functionally expressing the hs3b/hs4-deficient allele were dramatically outclassed by B cells expressing the wild-type locus and normally switching to IgA. This study thus also highlights the role of germinal centers in the competition between B cells for affinity maturation and suggests that membrane IgA may promote recruitment in an activated B-cell compartment, or proliferation of activated B cells, more efficiently than IgM in Peyer patches.

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