Genome-wide screens identify calcium signaling as a key regulator of IgE+ plasma celldifferentiation and survival
Newman, R.; Tolar, P.
Show abstract
IgE antibodies protect against toxins and parasites, however, they also mediate allergic reactions. In contrast to other antibody isotypes, B cells switched to IgE respond transiently and do not give rise to long-lived plasma cells (PCs) or memory B cells. Although the intrinsic differences of IgE+ B cells have been linked to signaling by the IgE-B cell receptor (BCR), the molecular pathways controlling their behavior remain poorly understood. Here we employ whole-genome CRISPR screening to identify genes regulating IgE+ B cell proliferation, survival and differentiation into PCs. We show that IgE+ B cells are selectively suppressed by the IgE-BCR signaling to intracellular calcium, which inhibits PC differentiation and limits their lifespan after differentiation. Consequently, manipulation of calcium signaling in vivo enhances IgE+ PC responses. Insights from this pathway shed new light on the self-limiting character of IgE responses and open new avenues to eliminate IgE+ PCs in allergy.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Protein kinase Cδ is essential for the IgG response against T cell-independent type 2 antigens and commensal bacteria 96%
- The Structure-Selective Endonucleases GEN1 and MUS81 are Functionally Complementary in Safeguarding the Genome of Proliferating B Lymphocytes 95%
- Orai3 and Orai1 are essential for CRAC channel function and metabolic reprogramming in B cells 95%
Similar papers in this journal
- Negative feedback by NUR77/Nr4a1 restrains B cell clonal dominance during early T-dependent immune responses 97%
- STAT3 signaling in B cells controls germinal center zone organization and recycling 96%
- Uncontrolled CD21low age-associated and B1 B cell accumulation caused by failure of an EGR2/3 tolerance checkpoint 96%
Similar papers in this journal
- Pdap1 protects mature B lymphocytes from stress-induced cell death and promotes antibody gene diversification 96%
- B Cell Division Capacity in Germinal Centers Depends on Myc Transcript Stabilization Through m6A mRNA Methylation and IGF2BP3 Functions 96%
- IRF7 controls spontaneous autoimmune germinal center and plasma cell checkpoints 96%
Similar papers in this journal
- Identification of a novel enhancer essential for Satb1 expression in TH2 cells and activated ILC2s. 95%
- STAT5B leukemic mutations, altering SH2 tyrosine 665, have opposing impacts on immune gene programs 94%
- ICOS costimulation is indispensable for the differentiation of T follicular regulatory cells 94%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.