Early derivation of IgM memory cells and bone marrow plasmablasts

Area of Science:

• Immunology
• B cell biology
• Infectious disease

Background:

• IgM memory B cells are crucial for adaptive immunity in mice and humans.
• Previous studies identified CD11c-positive IgM memory cells and bone marrow antibody-secreting cells (ASCs) after infection, but their origins were unclear.

Purpose of the Study:

• To elucidate the origins and maintenance mechanisms of distinct IgM-positive B cell populations generated during ehrlichial infection.
• To identify early precursor B cells expressing activation-induced cytidine deaminase (AID).

Main Methods:

• Utilized an AID-regulated tamoxifen-inducible Cre-recombinase-EYFP reporter mouse model.
• Administered tamoxifen at various time points post-infection to trace cell lineages.
• Analyzed cell populations for T-bet expression, somatic hypermutation, and AID transcription.
• Investigated the role of CD4 T cells and Toll-like receptor (TLR) signaling.

Main Results:

• Two distinct long-term IgM-positive B cell populations, IgM memory cells and bone marrow ASCs, were identified early post-infection.
• IgM memory cells, unlike bone marrow IgM ASCs, required CD4 T cell help for AID transcription and underwent somatic hypermutation.
• Bone marrow IgM ASCs were elicited independently of T cell help and TLR signaling.
• AID was constitutively expressed in IgM memory cells but not in bone marrow ASCs.

Conclusions:

• Distinct mechanisms govern the generation and maintenance of long-term IgM-positive B cell populations.
• These findings reveal a more complex picture of B cell memory development following infection.