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The xid mutation diminishes memory B cell generation but does not affect somatic hypermutation and selection
A Ridderstad1, G J Nossal, D M Tarlinton
1The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Journal of Immunology (Baltimore, Md. : 1950)
|October 15, 1996
Summary
Mice with the xid gene mutation show a reduced primary immune response due to fewer antibody-forming cells and memory B cells. However, their secondary immune response is normal, suggesting memory B cell numbers are sufficient.
Area of Science:
- Immunology
- Genetics
Background:
- The xid gene mutation in mice impairs T cell-dependent immune responses.
- Understanding the impact of xid on B cell memory is crucial for immune response studies.
Purpose of the Study:
- To investigate the relationship between primary and secondary T cell-dependent immune responses in xid mice.
- To determine the role of the xid gene in B cell memory formation and affinity maturation.
Main Methods:
- Utilized the response of xid mice to (4-hydroxy-3-nitrophenyl)acetyl (NP) hapten as a model.
- Assessed antibody-forming cell (AFC) generation, germinal center reactions, and memory B cell frequency.
- Analyzed somatic mutations in V(H) genes of B cells during secondary responses.
Main Results:
- Xid mice exhibited a significantly reduced primary immune response with decreased AFC generation and germinal center reactions.
- A 10-fold reduction in NP-specific memory B cells was observed in xid mice prior to secondary immunization.
- Despite lower memory B cell frequency, secondary exposure to antigen elicited a normal quantitative and qualitative immune response in xid mice, comparable to wild-type mice.
- Affinity maturation, assessed by somatic mutations in V(H) genes, was normal in xid secondary response B cells.
Conclusions:
- The xid gene product is not essential for affinity maturation processes.
- While xid mice generate memory B cells at a lower frequency, this reduction does not compromise the magnitude of the secondary immune response.
- The results suggest that the reduced memory B cell frequency in xid mice remains above a critical threshold required for a normal secondary immune response.