Two waves of memory B-cell generation in the primary immune response

Area of Science:

• Immunology
• Cell Biology

Background:

• Memory B cells are crucial for long-term immunity.
• Germinal center (GC) formation and affinity maturation are known pathways for memory B cell generation.
• The role of GC-independent pathways in normal mice is not well understood.

Purpose of the Study:

• To investigate the contribution of GC-independent memory B cell generation in normal mice.
• To determine if manipulating GC formation affects memory B cell development and antibody production.

Main Methods:

• Administration of anti-inducible co-stimulator (ICOS) monoclonal antibodies (mAbs) during the primary immune response in mice.
• Analysis of GC B cell generation, somatic mutation accumulation in IgV(H) genes, and affinity maturation.
• Assessment of memory B cell generation, antibody production, and secondary response reconstitution.

Main Results:

• Anti-ICOS treatment inhibited GC B cell generation but did not affect IgG1 memory B cells or long-term IgG1 antibody production.
• GC B cells in treated mice showed somatic mutations and affinity maturation.
• Memory B cells accumulated few mutations and mediated a low-affinity secondary response, indicating GC-independent generation.

Conclusions:

• Memory B cells are generated via two distinct pathways: one involving GC reactions and affinity maturation, and another independent of these processes.
• The GC-independent pathway generates low-affinity memory B cells.
• Low-affinity memory B cells can contribute to long-term antibody production and sustained immunity.