TCR+/BCR+ "double expresser" cells and their associated public B cell clone are not enriched in type 1 diabetes

Ahmed and colleagues recently described a novel hybrid lymphocyte that expresses both a B cell receptor and a T cell receptor, which they termed double expresser (DE) cells. They reported that DE cells were associated with type 1 diabetes (T1D), being present at increased numbers in the peripheral blood of T1D subjects compared to controls, and that DE cells were enriched for a public B cell clonotype that may contribute to autoimmune responses in T1D. Here we describe our efforts to reproduce and extend some of their findings. While we were able to identify events matching the DE phenotype by flow cytometry at low abundance, we found no association between the frequency of DE cells and T1D status. In addition, we found no enrichment of DE cells in the spleen, superior mesenteric artery lymph node, mesenteric lymph node or pancreatic lymph nodes from organ donors with and without T1D. We also were unable to identify the public clone-associated third complementarity determining region (CDR3) sequence or any similar CDR3 sequence, in bulk populations or in sorted DE cells from individuals with T1D or from controls. We also did not observe increased usage of the public clone VH4-38-02 or DH5-18|5-5 or VH/DH combination in B cells or in sorted DE cells. Finally, we comment on technical concerns with the data generated by Ahmed and colleagues. Taken together, our results and analyses of their data favor the interpretation that DE cells are the result of technical artifacts and that DE cells as well as their public clonotype are not enriched in T1D.