X lymphocyte
An X lymphocyte (X cell, dual expressers or DE cells) is a type of white blood cells, hybrid lymphocyte that combine properties of both conventional lymphocytes - T cell and B cell. Existence of X cells was confirmed by only one research group so far in 2019.[1] They found lymphocytes that have on their surface functional both B cell receptor (BCR) and T cell receptor (TCR) and express several genes typical only for T cells or B cells. That's the reason, why these cells are called dual expressers (DE) or dual expresser cells. It is unknow when and where in the body they develope or if they have some function in healthy organism.
It is possible that DE cells could play role in development of type I diabetes,[1][2] although some scientists doubt about the first evidence[3] and more data is needed.
= Discovery and potential role in type I diabetes '[edit]
DE cells were described during[blood analysis of type I diabetes patients, when the researcheres were looking for another cell type originally.[2] What's more, diabetes patients had more DE cells in their blood than healthy people. Firstly they confirmed with several methods, that DE cells really express functional both BCR and TCR even if the cells were activated. Then they examined variability of these receptors. Conventional B cells have broad repertoire of BCR, and so did DE cells from healthy participants. But almost all DE cells from diabetes patients had the same clonotype (same DNA sequence of variable part of the receptor), which they've called x-clonotype.[1][2][3]
About type I diabetes is known, that T helper lymphocytes in cooperation with B cells and APCs wrongly recognise insulin as dangerous peptide. Then cytotoxic T cells are activated and destroy all insulin producing beta cells of pancreas. Insulin is presented for immune cells on HLA complex, whereas one of the risk factors of developing type I diabetes is the variant HLA-DQ8.[4] Remaining question is why is insulin recognised by T cells in the first place. Authors of the study suggest that T cell recognition of DQ8 in bond with insulin is preceded by recognition of DQ8 in bond with peptide encoded by x-clonotype of DE cells. Bond of DQ molecule with this peptide has much higher immunogenicity than bond with insulin and so this peptide could serve to T cells as first autoantigen.[1][2]
If this theory is true, we would be able to use x-clonotype to screening patients in the future or we would even eliminate DE cells to protect patients from developing diabetes, according to the authors.[1][2]
References[edit]
- ↑ 1.0 1.1 1.2 1.3 1.4 Ahmed, Rizwan; Omidian, Zahra; Giwa, Adebola; Cornwell, Benjamin; Majety, Neha; Bell, David R.; Lee, Sangyun; Zhang, Hao; Michels, Aaron; Desiderio, Stephen; Sadegh-Nasseri, Scheherazade (2019-05-30). "A Public BCR Present in a Unique Dual-Receptor-Expressing Lymphocyte from Type 1 Diabetes Patients Encodes a Potent T Cell Autoantigen". Cell. 177 (6): 1583–1599.e16. doi:10.1016/j.cell.2019.05.007. ISSN 0092-8674. PMC 7962621 Check
|pmc=value (help). PMID 31150624. - ↑ 2.0 2.1 2.2 2.3 2.4 "Newly Discovered Immune Cell Linked to Type 1 Diabetes". Johns Hopkins Medicine Newsroom. 2019-05-30. Retrieved 2020-01-22.
- ↑ 3.0 3.1 "Novel Type of Immune Cell Discovered in Type 1 Diabetes Patients". The Scientist Magazine®. Retrieved 2020-01-22.
- ↑ van Lummel, Menno; van Veelen, Peter A.; Zaldumbide, Arnaud; de Ru, Arnoud; Janssen, George M. C.; Moustakas, Antonis K.; Papadopoulos, George K.; Drijfhout, Jan W.; Roep, Bart O.; Koning, Frits (2012-03-16). "Type 1 Diabetes-associated HLA-DQ8 Transdimer Accommodates a Unique Peptide Repertoire". Journal of Biological Chemistry. 287 (12): 9514–9524. doi:10.1074/jbc.M111.313940. ISSN 0021-9258. PMC 3308765. PMID 22184118.
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