Involvement of activation induced cytidine deaminase in malignant B-cells expressing two distinct M-components as an etiology of biclonal gammopathy

Biclonal gammopathy (BG) is a rare phenomenon in which 2 M proteins are detected in the same patient, with 2 major hypotheses regarding its etiology. One potential explanation is that completely different malignant B-cell clones produce different M proteins, while the other is that there is a malignant clone that produces both M proteins simultaneously. In this study, we examined 2 cases of B-cell malignancy with BG and found that some cells were double positive for both M proteins by immunofluorescence and flow cytometry. However, most of the remaining cells were single positive cells that produced only one of the M proteins. We hypothesized that double positive cells were in the process of transitioning from 1 single positive cell to another single positive cell, and that class switch recombination (CSR) would be involved as a mechanism. We then examined the expression of activation induced cytidine deaminase (AICDA), which is responsible for CSR, and found that lymphoma/myeloma cells in 2 BG patients were positive for AICDA by immunostaining. Our study is the first report suggesting that AICDA may be involved in the pathogenesis of BG.

Automated summary

Biclonal gammopathy is a rare phenomenon characterized by the detection of 2 M proteins in the same patient. The etiology of this condition remains unclear. In this study, we found double positive cells in two cases of B-cell malignancy with biclonal gammopathy, suggesting a possible involvement of cell transition and class switch recombination. Immunostaining revealed the expression of activation induced cytidine deaminase in these cells, indicating its potential role in the pathogenesis of biclonal gammopathy.