Hayakawa et al. show that distinctive B-lineage progression from B-1 development allows for generation of B1a cells with restricted BCRs and self-renewal capacity, both contributing to potential for CLL progression.

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Expression of a germline VH3609/D/JH2 immunoglobulin heavy chain in mice results in the generation of B1 B cells with anti-thymocyte/Thy-1 glycoprotein autoreactivity (ATA) by co-expression of Vk21-5/Jk2 light chain leading to production of serum IgM natural autoantibody. In these same mice, the marginal zone B cell (MZ B) subset in spleen shows biased usage of a set of immunoglobulin light chains different from B1 B cells, with 30% having an identical Vk19-17/Jk1 light chain rearrangement. This VH3609/Vk19-17 IgM is reactive with intestinal goblet cell granules, binding to the intact large polymatrix form of mucin 2 glycoprotein secreted by goblet cells. Analysis of a μκBCR transgenic mouse with this anti-goblet cell/mucin2 autoreactive specificity (AGcA) demonstrates that immature B cells expressing the transgenic BCR become marginal zone B cells in spleen by T cell-independent BCR signaling. These transgenic B cells produce AGcA as the predominant serum IgM, but without enteropathy. Without the transgene, AGcA autoreactivity is low but detectable in the serum of BALB/c and C.B17 mice, and this autoantibody is specifically produced by the MZ B cell subset. Thus, our findings reveal that AGcA is a natural autoantibody associated with MZ B cells.

Cell therapy using mesenchymal stem cells (MSCs) is used as effective regenerative therapy. Cell therapy requires effective cell separation without cell modification and cell activity sustainment. In this study, we...