Dysregulation of of phospholipid-specific phagocytosis by B1 B cells in diet-induced obese mice

B1 B cells have received increasing attention recently due to their newly discovered phagocytic and microbicidal capabilities. Several studies have demonstrated that B1 cells can phagocytize polystyrene fluorescent particles, bacteria (Staphylococcus aureus, Escherichia coli), and even apoptotic cells. Nevertheless, little is known about the biological significance of this seemingly redundant function of B1 B cells as compared to that of conventional phagocytes. Here we investigate the unique phosphotidylcholine (PtC)-specific B1 B cell phagocytosis. PtC is a major phospholipid in the biological membrane and a classical antigen recognized by B1 B cell-derived natural antibodies. These antibodies play important roles in immune defense as well as tissue homeostasis. Here we report that B1 cells preferentially phagocytose PtC-coated beads, differing from that of conventional macrophages. We further attest that these beads were truly internalized and subsequently fused with hydrolytic lysosomes indicated by increasing fluorescent intensity of a pH-sensitive dye. Despite the differences in antigen specificity, phagocytosis of both B1 cells and macrophages can be inhibited by the microtubule-inhibitor, Colchicine, in a dose-dependent manner. Most intriguingly, upon chronic high-fat diet (HFD) consumption by the host, B1 cell phagocytosis starts to lose antigen-specificity for PtC. Morphologically, some of these B1 B cells in DIO mice show enlarged cytosol and engulfed more beads, indicating a transition to macrophage-like cells. Our study suggests for the first time that B1 B cells have unique phospholipid-specific phagocytosis capacity, which is affected by diet-induced obesity

Renormalization Group Fixed Point with a Fourth Generation: Higgs-induced Bound States and Condensates

In the Standard Model with four generations, the two-loop renormalization group equations for the Higgs quartic and Yukawa couplings have a fixed point structure. If the masses of the fourth family are sufficiently heavy, it will contain a natural scale $\Lambda_{FP}$ in the range of a few TeV to the order of $10^2$ TeV, above which the Higgs quartic and Yukawa couplings become practically constant. We found that around $\Lambda_{FP}$ the strong Yukawa couplings make it possible for the fourth generation to form bound states, including composite extra Higgs doublets. In this scenario the fourth generation condensates are obtained without introducing Technicolor or other unknown interactions.Comment: 22 pages, 10 figure