B-1 derived anti-Thy-1 B cells in old aged mice develop lymphoma/leukemia with high expression of CD11b and Hamp2 that different from TCL1 transgenic mice

Abstract

Human old aged unmutated chronic lymphocytic leukemia U-CLL are the TCL1⁺ZAP70⁺CD5⁺ B cells. Since CD5 makes the BCR signaling tolerance, ZAP70 increased in U-CLL not only TCL1⁺ alone. In mice, TCL1 (TCL1A) is the negative from neonate to old aged, as TC^-. V_H8-12/V_k21-5 is the anti-thymocyte/Thy-1 autoreactive ATA B cell. When ATA μκTg generation in mice, ATA B cells are the neonate generated CD5⁺ B cells in B-1, and in the middle age, CD5⁺ can be down or continuously CD5⁺, then, old aged CLL/lymphoma generation with increased CD11b in TC^-ZAP70^-CD5^- or TC^-ZAP70⁺CD5⁺. In this old aged TC^-ATA B microarray analysis showed most similar to human CLL and U-CLL, and TC^-ZAP70⁺CD5⁺ showed certain higher present as U-CLL. Original neonate ATA B cells showed with several genes down or further increase in old aged tumor, and old aged T-bet⁺CD11c⁺, CTNNB1^hi, HMGB^hi, CXCR4^hi, DPP4^hi and decreased miR181b. These old aged increased genes and down miR181b are similar to human CLL. Also, in old age ATA B cell tumor, high CD38⁺⁺CD44⁺⁺, increased Ki67⁺ AID⁺, and decreased CD180^- miR15O^low are similar to U-CLL. In this old aged ATA B, increased TLR7,9 and Wnt10b. TC⁺Tg generated with ATAμκTg mice occurred middle age tumor as TC⁺ZAP70^-CD5⁺ or TC⁺ZAP70⁺CD5⁺, with high NF-kB1, TLR4,6 and Wnt5b,6 without increased CD11b. Since neonatal state to age with TC⁺Tg continuously, middle age CLL/lymphoma generation is not similar to old aged generated, however, some increased in TC⁺ZAP70⁺ are similar to the old age TC^- ATA B tumor. Then, TC^- ATA B old age tumor showed some difference to human CLL. ATA B cells showed CD11b⁺CD22⁺⁺, CD24 down, and hepcidin Hamp2⁺⁺ with iron down. This mouse V8-12 similar to human V2-5, and V2-5 showed several cancers with macrophages/neutrophils generated hepcidin⁺ iron^low or some showed hepcidin^- iron⁺ with tumor, and mouse V8-12 with different V_k19-17 generate MZ B cells strongly increased macrophage⁺⁺ in old aged and generated intestine/colon tumor. Conclusion, neonate generated TC^-ATA B1 cells in old aged tumor generation are CD11b⁺ in the leukemia CLL together with lymphoma cancer with hepcidin-related Hamp2⁺⁺ in B-1 cell generation to control iron.

Keywords: B1; CD11b; CLL/lymphoma; Hamp2; TC+ Tg; V2-5.