scholarly journals Identification of a T follicular helper cell subset that drives anaphylactic IgE

Science ◽  
2019 ◽  
Vol 365 (6456) ◽  
pp. eaaw6433 ◽  
Author(s):  
Uthaman Gowthaman ◽  
Jennifer S. Chen ◽  
Biyan Zhang ◽  
William F. Flynn ◽  
Yisi Lu ◽  
...  
Keyword(s):  
B Cells ◽  
Immunoglobulin E ◽  
Cell Subset ◽  
Specific Ige ◽  
Interleukin 4 ◽  
Cellular Mechanisms ◽  
Follicular Helper ◽  
Helper Cell Subset ◽  
Life Threatening ◽  
T Follicular Helper Cell

Cross-linking of high-affinity immunoglobulin E (IgE) results in the life-threatening allergic reaction anaphylaxis. Yet the cellular mechanisms that induce B cells to produce IgE in response to allergens remain poorly understood. T follicular helper (TFH) cells direct the affinity and isotype of antibodies produced by B cells. Although TFH cell–derived interleukin-4 (IL-4) is necessary for IgE production, it is not sufficient. We report a rare population of IL-13–producing TFH cells present in mice and humans with IgE to allergens, but not when allergen-specific IgE was absent or only low-affinity. These “TFH13” cells have an unusual cytokine profile (IL-13hiIL-4hiIL-5hiIL-21lo) and coexpress the transcription factors BCL6 and GATA3. TFH13 cells are required for production of high- but not low-affinity IgE and subsequent allergen-induced anaphylaxis. Blocking TFH13 cells may represent an alternative therapeutic target to ameliorate anaphylaxis.

S.135. ICOSlowCXCR5intermediate T Follicular Helper Cell Subset Secretes the Largest Amounts of IL-21 upon Interaction with Naïve B cells

2009 ◽  
Vol 131 ◽  
pp. S169
Author(s):  
Salah Eddine Bentebibel ◽  
Nathalie Schmitt ◽  
Rimpei Morita ◽  
Jacques Banchereau ◽  
Hideki Ueno
Keyword(s):  
B Cells ◽  
Cell Subset ◽  
Helper Cell ◽  
Follicular Helper ◽  
Helper Cell Subset ◽  
T Follicular Helper Cell

scholarly journals Expansion of an osteopontin‐expressing T follicular helper cell subset correlates with autoimmunity in B6.Sle1b mice and is suppressed by the H1‐isoform of the Slamf6 receptor

2013 ◽  
Vol 27 (8) ◽  
pp. 3123-3131 ◽  
Author(s):  
Marton Keszei ◽  
Cynthia Detre ◽  
Wilson Castro ◽  
Erica Magelky ◽  
Michael O'Keeffe ◽  
...  
Keyword(s):  
Cell Subset ◽  
Helper Cell ◽  
Follicular Helper ◽  
Helper Cell Subset ◽  
T Follicular Helper Cell

scholarly journals Recombinant Dirofilaria immitis Polyprotein That Stimulates Murine B Cells To Produce Nonspecific Polyclonal Immunoglobulin E Antibody

2002 ◽  
Vol 70 (3) ◽  
pp. 1235-1244 ◽  
Author(s):  
Hiroyuki Tezuka ◽  
Shinjiro Imai ◽  
Riho Muto ◽  
Yuko Furuhashi ◽  
Koichiro Fujita
Keyword(s):  
B Cells ◽  
Dirofilaria Immitis ◽  
Immunoglobulin E ◽  
Polymyxin B ◽  
Specific Ige ◽  
Interleukin 4 ◽  
Interferon Production ◽  
Mitogenic Effect ◽  
Helminth Infections ◽  
Cd23 Expression

ABSTRACT Nonspecific immunoglobulin E (IgE) production is an event characteristically observed in parasitic helminth infections, but its mechanisms are still unclear. To define these mechanisms, we prepared a recombinant Dirofilaria immitis protein (rDiAg) and assessed its effect on nonspecific IgE production. rDiAg preferentially induced nonspecific IgE production, without eliciting specific IgE production, as well as a Th2-type cytokine profile (high interleukin-4 [IL-4] and IL-10 production but low gamma interferon production) in BALB/c mice. rDiAg significantly elicited the proliferative response of naive B cells. This response was not abolished by polymyxin B, an inhibitor of lipopolysaccharide (LPS), and rDiAg normally expanded splenic B cells from LPS nonresponder C3H/HeJ mice. Thus, the mitogenic effect of rDiAg was not due to LPS contamination. rDiAg also enhanced levels of CD23 expression on splenic B cells. Splenic B cells produced marked levels of IgE when cultured with the combination of rDiAg and IL-4 (rDiAg-IL-4), whereas peritoneal B cells produced negligible levels of IgE. rDiAg-IL-4-induced IgE production by splenic B cells was synergistically increased by coculture with peritoneal B cells. rDiAg-driven IL-10 secretion was higher in peritoneal B cells than in splenic B cells. IgE production by splenic B cells cocultured with peritoneal B cells was decreased to a level comparable to that by splenic B cells in the presence of a neutralizing anti-IL-10 monoclonal antibody. Collectively, these results suggest that rDiAg-induced polyclonal expansion and IgE class switching of splenic B cells contribute to nonspecific IgE production and that these responses are enhanced by peritoneal B-cell-derived IL-10.

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