Single cell clonal analysis identifies an AID-dependent pathway of plasma cell differentiation

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Germinal centers (GCs) are essential sites for B cell maturation, affinity improvement, and differentiation into memory B cells or antibody-secreting plasma cells.
• Activation-induced deaminase (AID) initiates somatic hypermutation and class switch recombination, critical processes in GC B cell development.

Purpose of the Study:

• To investigate the role of AID in the terminal differentiation of GC B cells into antibody-secreting plasma cells.
• To identify novel cell subsets involved in B cell differentiation pathways.

Main Methods:

• Single-cell transcriptome analysis in a mouse model tracing AID-experienced cells.
• Immunoglobulin clonal analysis to track B cell lineage relationships.
• Comparative analysis of wild-type and AID-deficient mice.

Main Results:

• Identification of a novel late-preplasmablast (L-prePB) cell subset with strong clonal ties to plasmablasts (PBs).
• AID deficiency alters GC B cell transcriptional cluster profiles and reduces the proportion of L-prePB cells.
• Impaired transition from L-prePB to PB subsets in mice lacking AID.

Conclusions:

• AID is essential for shaping the differentiation fate of GC B cells.
• AID facilitates the generation of plasma cells from a pre-plasmablast state.
• The L-prePB subset represents a key intermediate in AID-dependent B cell terminal differentiation.