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Sequential triggering of apoptosis, somatic mutation and isotype switch during germinal center development
Y J Liu1, C Arpin, O de Bouteiller
1Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
Seminars in Immunology
|June 1, 1996
Summary
This study identifies and isolates human peripheral B-cell subpopulations involved in B-cell maturation, including naive, germinal center, and memory B cells, using surface markers like CD38 and IgD.
Area of Science:
- Immunology
- Cell Biology
Background:
- B-lymphocyte development is crucial for adaptive immunity.
- Understanding peripheral B-cell maturation in secondary lymphoid tissues is essential.
Purpose of the Study:
- To analyze the peripheral B-cell maturation pathway in human tonsils.
- To identify and isolate distinct B-cell subpopulations based on surface antigen expression.
Main Methods:
- Analysis of surface antigen expression (sIgD, CD38, CD77) on tonsillar B lymphocytes.
- Phenotypic, functional, and Ig gene analysis (IgV gene sequences, sterile transcripts, DNA switch circles).
Main Results:
- Identified six B-cell subpopulations: naive, germinal center founder, germinal center, centroblasts, centrocytes, and memory B cells.
- Characterized these subpopulations by their expression of sIgD, CD38, and CD77, and their stage in somatic mutation and isotype switching.
- Observed high somatic mutation accumulation in germinal center B cells and activated somatic mutation machinery in centroblasts.
Conclusions:
- Human peripheral B-cell subpopulations representing distinct differentiation stages have been identified and isolated.
- These stages include phases before, during, and after apoptosis, somatic mutation, and isotype switching.
- Surface markers sIgD and CD38 are key for delineating these critical B-cell maturation steps.