Enhanced Mott cell formation linked with IgM Fc receptor (FcμR) deficiency

Area of Science:

• Immunology
• Cell Biology

Background:

• Mott cells are unusual plasma cells with intracytoplasmic immunoglobulin inclusions.
• Previous studies noted increased Mott cells in a specific IgM Fc receptor (FcμR)-deficient mouse strain.
• Phenotypic discrepancies among different FcμR-deficient mouse models necessitated further investigation.

Purpose of the Study:

• To confirm if enhanced Mott cell formation is a general phenotype of FcμR deficiency.
• To investigate the role of FcμR in regulating Mott cell development and immunoglobulin inclusion formation.
• To analyze the genetic and functional aspects of Mott cells in FcμR-deficient B cells.

Main Methods:

• Comparative analysis of Mott cell formation in multiple FcμR-deficient (KO) and wild-type (WT) mouse strains.
• In vitro stimulation of splenic B cells with LPS or B-1/B-2 activation cocktails.
• Nucleotide sequence analysis of immunoglobulin variable regions in hybridoma clones.
• Functional studies involving FcμR cDNA transduction into Mott hybridoma cells.

Main Results:

• FcμR deficiency consistently led to enhanced Mott cell formation in peripheral lymphoid tissues across different mutant strains.
• Splenic B cells from FcμR KO mice generated significantly more Mott cells than WT mice upon stimulation.
• Sequence analysis revealed minimal somatic hypermutation in immunoglobulin genes of Mott cells from FcμR KO mice.
• Restoration of FcμR expression in Mott hybridoma cells reduced inclusion bodies and increased IgM secretion, with secreted IgM binding to FcμR.

Conclusions:

• FcμR deficiency is a general cause of enhanced Mott cell formation.
• FcμR plays a regulatory role in controlling the development of Mott cells and the formation of IgM-inclusion bodies.
• FcμR signaling may influence B cell differentiation pathways leading to plasma cell formation and immunoglobulin handling.