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Updated: Aug 9, 2026

Murine Model of CD40-activation of B cells
Published on: March 6, 2010
B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B
Rajendra N Damle1, Fabio Ghiotto, Angelo Valetto
1North Shore-Long Island Jewish Research Institute, Manhasset, NY 11030, USA.
Insights
B-cell chronic lymphocytic leukemia (B-CLL) cells exhibit characteristics of activated, antigen-experienced B lymphocytes, regardless of V gene mutation status. This suggests diverse antigen exposure histories in different B-CLL subgroups.
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- B-cell chronic lymphocytic leukemia (B-CLL) is typically viewed as a disease of resting, antigen-naive CD5(+) B lymphocytes.
- The precise activation and differentiation state of B-CLL cells remains a subject of investigation.
Purpose of the Study:
- To investigate whether B-CLL cells display phenotypes consistent with antigen-experienced and activated B cells.
- To compare the expression of activation and differentiation markers between B-CLL cells and normal B lymphocytes.
Main Methods:
- Flow cytometry analysis of CD5(+)CD19(+) cells from B-CLL patients and age-matched healthy donors.
- Assessment of cell surface marker expression, including CD23, CD25, CD69, CD71, CD27, CD22, Fcgamma receptor IIb, CD79b, and immunoglobulin D.
- Comparison of marker expression between B-CLL subgroups with and without immunoglobulin V gene mutations.
Main Results:
- Leukemic B-CLL cells universally overexpress activation markers (CD23, CD25, CD69, CD71) and underexpress markers associated with resting B cells (CD22, Fcgamma receptor IIb, CD79b, immunoglobulin D).
- B-CLL cells uniformly express CD27, a marker associated with memory B cells, indicating an antigen-experienced phenotype.
- Subgroups of B-CLL patients with and without V gene mutations exhibit distinct marker expression profiles (e.g., CD69, CD71, CD62L, CD40, CD39, HLA-DR), suggesting different antigenic stimulation histories.
Conclusions:
- All B-CLL cells, irrespective of V gene mutation status, possess phenotypes of activated and antigen-experienced B lymphocytes.
- Differences in immunoglobulin V genotype correlate with distinct marker expression and likely reflect varied antigen-encounter histories in B-CLL pathogenesis.
Abstract:
B-cell chronic lymphocytic leukemia (B-CLL) is considered an accumulative disease of antigen-naive CD5(+) B lymphocytes that circulate in the resting state. However, to evaluate the possibility that B-CLL cells resemble antigen-experienced and activated B cells, we analyzed the expression of markers of cellular activation and differentiation on CD5(+)CD19(+) cells from B-CLL patients and from age-matched healthy donors. The leukemic cells from all B-CLL patients, including those that lack significant numbers of V gene mutations, bear the phenotype of activated B cells based on the overexpression of the activation markers CD23, CD25, CD69, and CD71 and the underexpression of CD22, Fcgamma receptor IIb, CD79b, and immunoglobulin D that are down-regulated by cell triggering and activation. Furthermore, these leukemic cells resemble antigen-experienced lymphocytes in the underexpression of molecules that are down-regulated by cell triggering and in the uniform expression of CD27, an identifier of memory B cells. A comparison of the phenotypes of B-CLL patients with and without immunoglobulin V gene mutations suggests that the 2 subgroups differ both in specific marker expression (CD69, CD71, CD62 L, CD40, CD39, and HLA-DR) and in the time since antigenic stimulation, based on the reciprocal relationship of CD69 and CD71 expression. These findings imply that the leukemic cells from all B-CLL cases (irrespective of V gene mutations) exhibit features of activated and of antigen-experienced B lymphocytes and that the B-CLL cells that differ in immunoglobulin V genotype may have different antigen-encounter histories.
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