Clonal relationships of memory B cell subsets in autoimmune mice

Area of Science:

• Immunology
• Cellular Biology
• Autoimmunity

Background:

• Immunological memory, comprising cellular and humoral arms, protects against re-infection via memory B cells (MBCs), plasma cells, and antibodies.
• While MBC subsets are characterized in immunized wildtype (WT) mice, their heterogeneity in autoimmune conditions remains less understood.

Purpose of the Study:

• To investigate the heterogeneity of the MBC compartment in autoimmune mouse models.
• To examine clonal relationships between MBC subsets and germinal center (GC) B cells in autoimmune models.

Main Methods:

• Analysis of MBC subsets based on CD73, CD80, and PD-L2 expression in surrogate light chain-deficient (SLC-/-), MRL, and MRLlpr/lpr mice.
• High-throughput sequencing of Ig heavy chains in SLC-/- mice.
• Lineage tree analyses of expanded clones.

Main Results:

• At least four MBC subsets were identified in autoimmune models (most expressing IgM) and WT mice.
• In SLC-/- mice, CD73-positive MBC subsets showed higher mutation frequencies.
• Lineage tree analyses revealed clonal overlaps between MBC subsets and GC B cells, with MBCs acting as both ancestors and progeny of GC B cells.

Conclusions:

• Multiple MBC subsets exist in both autoimmune and WT mice.
• These MBC subsets are clonally related to each other and to GC B cells in autoimmune models.
• Findings suggest that diverse MBC subsets can contribute to the GC reaction.