A functional BCR in human IgA and IgM plasma cells.

Area of Science:

• Immunology
• Cell Biology

Background:

• Plasma cells (PCs) are terminally differentiated B lymphocytes responsible for high-rate antibody secretion.
• PCs were traditionally considered to lack B-cell receptor (BCR) expression.
• Existing knowledge did not detail functional BCR expression differences across human antibody isotypes in PCs.

Purpose of the Study:

• To investigate the expression and function of the B-cell receptor (BCR) on human IgA, IgM, and IgG plasma cells (PCs).
• To determine if BCR signaling pathways are active in different human PC subsets.
• To explore the functional consequences of BCR expression on PC survival and potential implications for mucosal immunity.

Main Methods:

• Flow cytometry to detect BCR expression on human IgA, IgM, and IgG PCs.
• Stimulation of PCs with BCR cross-linking agents.
• Measurement of intracellular calcium (Ca2+) mobilization.
• Analysis of downstream signaling pathways including ERK1/2 and AKT phosphorylation.
• Assessment of PC survival rates under different conditions.

Main Results:

• Human IgA and IgM PCs, but not IgG PCs, express a membrane-bound, functional BCR complexed with the Igα/Igβ heterodimer.
• BCR cross-linking on IgA and IgM PCs induced Ca2+ influx and phosphorylation of ERK1/2 and AKT.
• BCR signaling influenced the survival of IgA PCs.
• Significant functional differences were identified between human IgG, IgM, and IgA PCs.

Conclusions:

• Human IgA and IgM plasma cells possess a functional BCR, challenging previous assumptions.
• BCR signaling in IgA PCs impacts their survival, suggesting a role in immune regulation.
• These findings highlight distinct mechanisms governing different human PC subsets.
• The antigen-specific modulation of the IgA PC repertoire may influence mucosal immune responses.