To B, or not to B: Is calcium the answer?

Area of Science:

• Immunology
• Cell Biology
• Calcium Signaling

Background:

• B lymphocytes are crucial for adaptive and innate immunity, mediating antibody secretion and antigen presentation.
• Dysfunctional B cells are implicated in autoimmune diseases, paraneoplastic syndromes, and immunodeficiencies.
• B cell receptor (BCR) signaling, including store-operated Ca2+ entry (SOCE), is vital for B cell development, survival, and function.

Purpose of the Study:

• To investigate the role of stromal interaction molecule (STIM) 1 and 2 in B cell survival and proliferation.
• To elucidate the impact of impaired SOCE on B cell signaling pathways.
• To explore compensatory mechanisms for B cell survival in the absence of functional SOCE.

Main Methods:

• Utilized B cells genetically deficient in STIM1 and STIM2.
• Assessed B cell survival, proliferation, gene expression, and signaling pathway activation (mTORC1, c-Myc).
• Investigated the effects of costimulatory signals (CD40, TLR9) on B cell function in STIM-deficient cells.

Main Results:

• B cells lacking STIM1 and STIM2 exhibit abolished SOCE, leading to impaired survival and proliferation.
• Absence of SOCE results in reduced expression of anti-apoptotic genes.
• Activation of mTORC1 and c-Myc signaling pathways is blunted in STIM-deficient B cells.
• Costimulation via CD40 or TLR9 can partially rescue B cell survival and proliferation.

Conclusions:

• STIM1 and STIM2-dependent SOCE is essential for maintaining B cell survival and proliferation.
• SOCE regulates critical checkpoints for B cell homeostasis through gene expression and signaling.
• CD40 and TLR9 costimulation offer potential therapeutic avenues to bypass SOCE-dependent B cell defects.