How many specific B cells are needed to protect against a virus?

Area of Science:

• Immunology
• Virology

Background:

• The antibody (Ab) repertoire size is theoretically vast, ranging from 10^4 to over 10^10 specificities.
• Estimating the protective anti-viral Ab repertoire is crucial for understanding immune responses.

Purpose of the Study:

• To estimate the size of the anti-viral protective Ab repertoire in mice against vesicular stomatitis virus (VSV).
• To analyze B cell and Ab-forming cell (AFC) frequencies and protective neutralizing Ab levels during VSV infection.

Main Methods:

• Analysis of AFC frequencies and neutralizing Ab levels during VSV infection.
• Limiting dilution assays and adoptive transfer experiments to SCID mice.
• Protection assays in SCID mice to determine protective Ab concentrations.

Main Results:

• During acute VSV infection, over 50% of IgG2a-producing AFCs were VSV-specific, recognizing neutralizing determinants.
• In later phases, VSV-specific AFCs decreased 10-20 fold, to about 1:10^4 spleen cells.
• Protective Ab concentrations were found to be 1-10 micrograms Ab/ml serum.

Conclusions:

• The neutralizing anti-viral protective memory-AFC repertoire against VSV is limited, estimated at 10^2 to 10^4 specificities.
• This suggests a focused immune response, with a small subset of AFCs maintaining long-term protection.