B cell receptor-induced apoptosis in primary transitional murine B cells: signaling requirements and modulation by T cell help [In Process Citation]

IgE can trigger potent allergic responses, yet the mechanisms regulating IgE production are poorly understood. Here we reveal that IgE+ B cells are constrained by chronic activity of the IgE B cell receptor (BCR). In the absence of cognate antigen, the IgE BCR promoted terminal differentiation of B cells into plasma cells (PCs) under cell culture conditions mimicking T cell help. This antigen-independent PC differentiation involved multiple IgE domains and Syk, CD19, BLNK, Btk, and IRF4. Disruption of BCR signaling in mice led to consistently exaggerated IgE+ germinal center (GC) B cell but variably increased PC responses. We were unable to confirm reports that the IgE BCR directly promoted intrinsic apoptosis. Instead, IgE+ GC B cells exhibited poor antigen presentation and prolonged cell cycles, suggesting reduced competition for T cell help. We propose that chronic BCR activity and access to T cell help play critical roles in regulating IgE responses.

Download Full-text

B-cell receptor signaling and CD40 ligand-independent T cell help cooperate in Helicobacter-induced MALT lymphomagenesis

Leukemia ◽

10.1038/leu.2010.76 ◽

2010 ◽

Vol 24 (6) ◽

pp. 1186-1196 ◽

Cited By ~ 54

Author(s):

V J Craig ◽

S B Cogliatti ◽

I Arnold ◽

C Gerke ◽

J-E Balandat ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Cell Receptor ◽

Cd40 Ligand ◽

B Cell Receptor ◽

Receptor Signaling ◽

B Cell Receptor Signaling ◽

T Cell Help ◽

Cell Receptor Signaling

Download Full-text

T cell hybridomas to study MHC-II restricted B-cell receptor-mediated antigen presentation by human B cells

Journal of Immunological Methods ◽

10.1016/j.jim.2011.05.005 ◽

2011 ◽

Vol 370 (1-2) ◽

pp. 35-42 ◽

Cited By ~ 2

Author(s):

Matthew B. Bartley ◽

David H. Canaday

Keyword(s):

T Cell ◽

B Cells ◽

B Cell ◽

Antigen Presentation ◽

Cell Receptor ◽

B Cell Receptor ◽

Mhc Ii ◽

Human B Cells

Download Full-text

Outer Periarteriolar Lymphoid Sheath Arrest and Subsequent Differentiation of Both Naive and Tolerant Immunoglobulin Transgenic B Cells Is Determined by B Cell Receptor Occupancy

Journal of Experimental Medicine ◽

10.1084/jem.186.5.631 ◽

1997 ◽

Vol 186 (5) ◽

pp. 631-643 ◽

Cited By ~ 57

Author(s):

Matthew C. Cook ◽

Antony Basten ◽

Barbara Fazekas de St. Groth

Keyword(s):

T Cell ◽

B Cells ◽

B Cell ◽

Receptor Occupancy ◽

Cell Receptor ◽

Antigen Concentration ◽

Identical Manner ◽

T Cell Help ◽

Self Antigen

T-dependent B cell responses in the spleen are initiated in the outer periarteriolar lymphoid sheath (PALS) and culminate in the generation of proliferative foci and germinal center reactions. By pulsing anti–hen egg lysozyme (HEL) immunoglobulin transgenic (IgTg) B cells with various concentrations of HEL in vitro before adoptive transfer into normal recipients, it was shown that a critical number of B cell receptors (BCRs) must be ligated for B cells to undergo arrest in the outer PALS. T cell help was manipulated independently of the BCR stimulus by incubating B cells expressing the appropriate major histocompatibility complex class II antigen with a peptide recognized by CD4+ TCR Tg T cells. B cells which either failed to arrest in the outer PALS due to a subthreshold BCR stimulus, or arrested only transiently due to the brevity of the BCR stimulus, underwent an abortive response within the follicles when provided with T cell help. In contrast, naive B cells stimulated by a sustained, suprathreshold concentration of either foreign or self-antigen and given T cell help, proliferated in the outer PALS and then differentiated. Outer PALS arrest was not influenced by the nature of the B cells occupying the follicle, but appeared to be determined solely by the magnitude of BCR stimulation. Thus antigen-pulsed B cells arrested in the outer PALS in an identical manner irrespective of whether the follicles comprised a population of normal B cells with multiple specificities, a monoclonal naive population, or a monoclonal population of tolerant B cells. In addition, tolerant B cells were found to relocate from the follicles to the outer PALS of HEL/anti-HEL double Tg mice in which the concentration of soluble self-antigen had been increased by zinc feeding. Similarly, when anti-HEL Tg mice were crossed with a second HEL Tg strain expressing a higher concentration of soluble HEL, the tolerant anti-HEL Tg B cells were located constitutively in the outer PALS. Thus, subtle variations in antigen concentration resulted in dramatic changes in positioning of B cells within the spleen. A series of mixed bone marrow chimeras in which the effective antigen concentration was inversely related to the number of self-reactive B cells due to absorption of antigen by transgene-encoded membrane and secreted Ig, was used to confirm that alteration in B cell position previously attributed to changes in follicular composition could be explained on the basis of available antigen concentration, rather than the diversity of the repertoire.

Download Full-text

Rapid Emergence of T Follicular Helper and Germinal Center B Cells Following Antiretroviral Therapy in Advanced HIV Disease

Frontiers in Immunology ◽

10.3389/fimmu.2021.752782 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chun-Shu Wong ◽

Clarisa M. Buckner ◽

Silvia Lucena Lage ◽

Luxin Pei ◽

Felipe L. Assis ◽

...

Keyword(s):

T Cell ◽

B Cells ◽

Antiretroviral Therapy ◽

B Cell ◽

Germinal Center ◽

Cell Receptor ◽

B Cell Receptor ◽

Cd4 T Cell ◽

Follicular Helper ◽

Cell Counts

Low nadir CD4 T-cell counts in HIV+ patients are associated with high morbidity and mortality and lasting immune dysfunction, even after antiretroviral therapy (ART). The early events of immune recovery of T cells and B cells in severely lymphopenic HIV+ patients have not been fully characterized. In a cohort of lymphopenic (CD4 T-cell count < 100/µL) HIV+ patients, we studied mononuclear cells isolated from peripheral blood (PB) and lymph nodes (LN) pre-ART (n = 40) and 6-8 weeks post-ART (n = 30) with evaluation of cellular immunophenotypes; histology on LN sections; functionality of circulating T follicular helper (cTfh) cells; transcriptional and B-cell receptor profile on unfractionated LN and PB samples; and plasma biomarker measurements. A group of 19 healthy controls (HC, n = 19) was used as a comparator. T-cell and B-cell lymphopenia was present in PB pre-ART in HIV+ patients. CD4:CD8 and CD4 T- and B-cell PB subsets partly normalized compared to HC post-ART as viral load decreased. Strikingly in LN, ART led to a rapid decrease in interferon signaling pathways and an increase in Tfh, germinal center and IgD-CD27- B cells, consistent with histological findings of post-ART follicular hyperplasia. However, there was evidence of cTfh cells with decreased helper capacity and of limited B-cell receptor diversification post-ART. In conclusion, we found early signs of immune reconstitution, evidenced by a surge in LN germinal center cells, albeit limited in functionality, in HIV+ patients who initiate ART late in disease.

Download Full-text

Notch1 enhances B-cell receptor-induced apoptosis in mature activated B cells without affecting cell cycle progression and surface IgM expression

Cell Death and Differentiation ◽

10.1038/sj.cdd.4401253 ◽

2003 ◽

Vol 10 (7) ◽

pp. 833-844 ◽

Cited By ~ 20

Author(s):

S Romer ◽

U Saunders ◽

H-M Jäck ◽

B M Jehn

Keyword(s):

Cell Cycle ◽

B Cells ◽

B Cell ◽

Cell Cycle Progression ◽

Cell Receptor ◽

B Cell Receptor ◽

Cycle Progression ◽

Induced Apoptosis ◽

Activated B Cells

Download Full-text

A critical role of TAK1 in B-cell receptor–mediated nuclear factor κB activation

Blood ◽

10.1182/blood-2008-08-176057 ◽

2009 ◽

Vol 113 (19) ◽

pp. 4566-4574 ◽

Cited By ~ 57

Author(s):

James Schuman ◽

Yuhong Chen ◽

Andrew Podd ◽

Mei Yu ◽

Hong-Hsing Liu ◽

...

Keyword(s):

T Cell ◽

B Cells ◽

B Cell ◽

Critical Role ◽

Cell Receptor ◽

Nuclear Factor Κb ◽

Cell Development ◽

B Cell Receptor ◽

Nuclear Factor

Abstract The kinase TAK1 is essential for T-cell receptor (TCR)–mediated nuclear factor κB (NF-κB) activation and T-cell development. However, the role of TAK1 in B-cell receptor (BCR)–mediated NF-κB activation and B-cell development is not clear. Here we show that B-cell–specific deletion of TAK1 impaired the transition from transitional type 2 to mature follicular (FO) B cells and caused a marked decrease of marginal zone (MZ) B cells. TAK1-deficient B cells exhibited an increase of BCR-induced apoptosis and impaired proliferation in response to BCR ligation. Importantly, TAK1-deficient B cells failed to activate NF-κB after BCR stimulation. Thus, TAK1 is critical for B-cell maturation and BCR-induced NF-κB activation.

Download Full-text