Local BLyS production by T follicular cells mediates retention of high affinity B cells during affinity maturation

Goenka, Radhika; Matthews, Andrew; Zhang, Bochao; O’Neill, Patrick J.; Scholz, Jean L.; Migone, Thi‐Sau; Leonard, Warren J.; Stohl, William; Hershberg, Uri; Cancro, Michael P.

doi:10.1084/jem.20130505

Cited by 104 publications

(111 citation statements)

References 58 publications

Supporting

Mentioning

107

Contrasting

Order By: Relevance

“…In contrast to the impaired B cell TACI expression, and in agreement with a recently reported study (34), we determined that the TACI ligand BAFF was significantly increased in the sera of XID mice. This inverse relationship between BAFF and TACI levels is also seen in newborn mice (28) and TACI KO mice (Fig.…”

Section: Discussionsupporting

confidence: 92%

Impaired B Cell Receptor Signaling Is Responsible for Reduced TACI Expression and Function in X-Linked Immunodeficient Mice

Uslu

Coleman

Allman

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

Immune response to T cell independent type 2 (TI-2) Ags, such as bacterial polysaccharides, is severely impaired in X-linked immunodeficient (XID) mice. In this study, we investigated the involvement of a proliferation-inducing ligand (APRIL) or BAFF and their receptors in the unresponsiveness of XID mouse to TI-2 Ags. We discovered that whereas serum BAFF levels were increased, the expression of the APRIL and BAFF receptor transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) was severely reduced in XID B cells. Moreover, B cells from XID mouse were unable to secrete Igs in response to APRIL or BAFF. In correlation with reduced TACI expression and impaired TACI function, APRIL or BAFF did not activate the classical NF-κB pathway in XID cells. Also correlating with the unaltered expression of BAFF receptor, BAFF stimulation induced the activation of the alternative NF-κB pathway in XID cells. Moreover, activation of MAPK pathway was ablated in APRIL-stimulated XID cells. Prestimulation of XID B cells with the TLR9 agonist, CpG led to a significant increase in TACI expression and restored TACI-mediated functions. CpG prestimulation also restored TACI-mediated signaling in APRIL- or BAFF-stimulated XID B cells. Finally, immunization of XID mouse with the prototype TI-2 Ag NP-Ficoll induced IgG and IgM Abs when CpG was given with NP-Ficoll. Collectively, these results suggest that reduced TACI expression is responsible for the unresponsiveness of XID mouse to TI-2 Ags and BCR activation controls TACI expression.

show abstract

Section: Discussionsupporting

confidence: 92%

Impaired B Cell Receptor Signaling Is Responsible for Reduced TACI Expression and Function in X-Linked Immunodeficient Mice

Uslu

Coleman

Allman

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…These results suggest that B cell-intrinsic TACI deficiency increases the availability of T cell help. In a recently published article, Goenka et al (30) showed that while the GC lacks BAFF, a TACI ligand, Tfh-derived BAFF contributes to persistence of B cell clones undergoing affinity maturation. Thus, enhanced recruitment of Tfh by TACI-deficient B cells may cause enhanced BAFF production at the T-B cell border, facilitating maintenance of expanded clones and selection of mutated B cells.…”

Section: Resultsmentioning

confidence: 99%

TACI deficiency enhances antibody avidity and clearance of an intestinal pathogen

Tsuji

Stein

Kamada³

et al. 2014

J. Clin. Invest.

View full text Add to dashboard Cite

“…An additional signal that may activate the alternative pathway in LZ B cells is stimulation by BAFF (38). Recent work provides evidence that Tfh cells secrete BAFF locally to adjacent LZ B cells (39). Of note, whereas abolishing BAFF secretion by Tfh cells impaired the selection of high-affinity GC B cells, it had no impact on the maintenance of the GC reaction.…”

Section: Discussionmentioning

confidence: 99%

Transcription factors of the alternative NF-κB pathway are required for germinal center B-cell development

Silva

Anderson

Carette

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The NF-κB signaling cascade relays external signals essential for B-cell growth and survival. This cascade is frequently hijacked by cancers that arise from the malignant transformation of germinal center (GC) B cells, underscoring the importance of deciphering the function of NF-κB in these cells. The NF-κB signaling cascade is comprised of two branches, the canonical and alternative NF-κB pathways, mediated by distinct transcription factors. The expression and function of the transcription factors of the alternative pathway, RELB and NF-κB2, in late B-cell development is incompletely understood. Using conditional deletion of relb and nfkb2 in GC B cells, we here report that ablation of both RELB and NF-κB2, but not of the single transcription factors, resulted in the collapse of established GCs. RELB/NF-κB2 deficiency in GC B cells was associated with impaired cell-cycle entry and reduced expression of the cell-surface receptor inducible T-cell costimulator ligand that promotes optimal interactions between B and T cells. Analysis of human tonsillar tissue revealed that plasma cells and their precursors in the GC expressed high levels of NF-κB2 relative to surrounding lymphocytes. Accordingly, deletion of nfkb2 in murine GC B cells resulted in a dramatic reduction of antigen-specific antibodysecreting cells, whereas deletion of relb had no effect. These results demonstrate that the transcription factors of the alternative NF-κB pathway control distinct stages of late B-cell development, which may have implications for B-cell malignancies that aberrantly activate this pathway.germinal center B cell | plasma cell | NF-κB transcription factors

show abstract

Local BLyS production by T follicular cells mediates retention of high affinity B cells during affinity maturation

Abstract: BLyS expression by GC follicular T cells is required for the efficient selection of high-affinity GC B cells.

Cited by 104 publications

References 58 publications

Impaired B Cell Receptor Signaling Is Responsible for Reduced TACI Expression and Function in X-Linked Immunodeficient Mice

Impaired B Cell Receptor Signaling Is Responsible for Reduced TACI Expression and Function in X-Linked Immunodeficient Mice

TACI deficiency enhances antibody avidity and clearance of an intestinal pathogen

Transcription factors of the alternative NF-κB pathway are required for germinal center B-cell development

Contact Info

Product

Resources

About