T Follicular Helper Cell-Germinal Center B Cell Interaction Strength Regulates Entry into Plasma Cell or Recycling Germinal Center Cell Fate

Ise, Wataru; Fujii, Kentaro; Shiroguchi, Katsuyuki; Ito, Ayako; Kometani, Kohei; Takeda, Kiyoshi; Kawakami, Eiryo; Yamashita, Kazuo; Suzuki, Kazuhiro; Okada, Takaharu; Kurosaki, Tomohiro

doi:10.1016/j.immuni.2018.03.027

Cited by 250 publications

(301 citation statements)

References 54 publications

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“…Overall, our findings are consistent with the previously discovered role of Ag-dependent BCR engagement in driving GC differentiation into PB. However, although in the previous study, T cell help has been shown to be critical for maturation and survival of the early GCPB (Kräutler et al, 2017), our findings are more consistent with another study (Ise et al, 2018) and suggest that an ongoing T cell help is required, even for the initial differentiation of GC B cells into PBs.…”

Section: Resultssupporting

confidence: 86%

B Cell Receptor Crosslinking Augments Germinal Center B Cell Selection when T Cell Help Is Limiting

Turner

Grigorova

2018

Cell Reports

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SUMMARY Antigen-dependent engagement of germinal center (GC) B cell receptors (BCRs) promotes antigen internalization and presentation for follicular helper T cells. However, whether BCR signaling is critical or synergistic with T cell help for GC B cell selection or differentiation is unclear. Here, by adapting an experimental approach that enables independent delivery of BCR-crosslinking antigen or T cell help to GC B cells in vivo, we showed that T cell help was sufficient to induce GC B cell expansion and plasmablast formation. However, although BCR crosslinking could not by itself promote GC B cell selection or differentiation, it could synergize with T cell help to enhance the GC and plasmablast responses when T cell help was limiting. These findings indicate that GC B cells can integrate variable inputs from T cell help and BCR signaling in vivo for an optimal process of selection and differentiation, critical for potent long-term humoral immunity.

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Section: Resultssupporting

confidence: 86%

B Cell Receptor Crosslinking Augments Germinal Center B Cell Selection when T Cell Help Is Limiting

Turner

Grigorova

2018

Cell Reports

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“…Smith et al first demonstrated by analyzing NP hapten-specific B-cell responses that the extent of affinity maturation differs between plasma cells and memory B cells. 25,27 Hence, the fate of GC B cells is highly correlated with their BCR affinity, and the high-affinity cells tend to be selected into the plasma cell pool. 23 .…”

Section: Pl a S Ma Cell S Elec Ti On During The G C Re Ac Ti Onmentioning

confidence: 99%

“…[36][37][38] In this system, extrinsic antigen is delivered to GC B cells via the C-type lectin endocytic receptor DEC205 (CD205), instead of via the BCR, and presentation of processed antigen peptide facilitates the interaction Krautler et al has recently suggested that the CD40 signal is dispensable for the generation of early plasma cells by using a CD40L blocking mAb in HEL-SRBC immunized mice. 27 Foxo1. 27 Foxo1.…”

Section: S I G Nal S That Induce G C B Cell S To B Ecome Pl a S Ma mentioning

confidence: 99%

“…Bcl6 lo cells with higher expression of IRF4 or Blimp-1 + are found among DZ GC B cells,27,32 suggesting that plasma cell precursors in the LZ migrate to the DZ and this accompanies their maturation toward plasma cells. Taken together, the c-Myc + Bcl6 lo IRF4 + cells are most likely to be plasma cell precursors that are in the process of curtailing the GC program and acquiring plasma cell identity, whereas the c-Myc + Bcl6 hi IRF4 − cells are GC recycling precursors (Figure 1).Given that the Bcl6 lo IRF4 + CD69 hi LZ GC cells do not express the plasma cell markers CD138 or Blimp-1, 27 these cells presumably represent the emerging, earliest plasma cell precursors.…”

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confidence: 99%

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Plasma cell differentiation during the germinal center reaction

Ise

Kurosaki

2019

Immunological Reviews

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Summary Germinal centers (GCs) are formed in secondary lymphoid tissues upon immunization with T‐dependent antigens. In GCs, somatic hypermutation generates B cells with increased antibody affinity and these high‐affinity B cells preferentially differentiate into plasma cells, which home to bone marrow and confer long‐lived humoral immunity. Recent studies have shed new light on the cellular and molecular basis for initiating the transition from a GC B cell to a plasma cell. Here, we review recent progress in our understanding of how plasma cell generation during the GC reaction is regulated for inducing effective long‐term protective immunity and for preventing harmful autoimmunity.

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“…98 Expression of IRF4 is important for the formation and function of GCs. Recent studies have suggested that high-affinity B cells in the light zone receive strong CD40 signals, downregulate BCL6, and exit the GC reaction as IRF4 + CD69 + cells that eventually differentiate into plasmablasts.…”

Section: Plasma Cellsmentioning

confidence: 99%

Plasma cells: You are what you eat

D'Souza

Bhattacharya

2019

Immunological Reviews

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Summary Plasma cells are terminally differentiated B lymphocytes that constitutively secrete antibodies. These antibodies can provide protection against pathogens, and their quantity and quality are the best clinical correlates of vaccine efficacy. As such, plasma cell lifespan is the primary determinant of the duration of humoral immunity. Yet dysregulation of plasma cell function can cause autoimmunity or multiple myeloma. The longevity of plasma cells is primarily dictated by nutrient uptake and non‐transcriptionally regulated metabolic pathways. We have previously shown a positive effect of glucose uptake and catabolism on plasma cell longevity and function. In this review, we discuss these findings with an emphasis on nutrient uptake and its effects on respiratory capacity, lifespan, endoplasmic reticulum stress, and antibody secretion in plasma cells. We further discuss how some of these pathways may be dysregulated in multiple myeloma, potentially providing new therapeutic targets. Finally, we speculate on the connection between plasma cell intrinsic metabolism and systemic changes in nutrient availability and metabolic diseases.

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T Follicular Helper Cell-Germinal Center B Cell Interaction Strength Regulates Entry into Plasma Cell or Recycling Germinal Center Cell Fate

Cited by 250 publications

References 54 publications

B Cell Receptor Crosslinking Augments Germinal Center B Cell Selection when T Cell Help Is Limiting

B Cell Receptor Crosslinking Augments Germinal Center B Cell Selection when T Cell Help Is Limiting

Plasma cell differentiation during the germinal center reaction

Plasma cells: You are what you eat

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