Type 1 Tindependent antigens

Type 1 antigens are directly mitogenic for B cells from certain species. LPS (lipopolysaccharide, endotoxin) of gram-negative bacteria is the proto-typic type 1 antigen for murine B cells. CD 14, a 55 kDa glycosylphosphatidylinositol (GPI)-anchored glycoprotein, is the major cell surface receptor for the activating effects of LPS on macrophages, B cells and various other cells. Serum lipid transfer protein or LPS-binding protein (LBP) accelerates the transfer of LPS to CD14 in a catalytic fashion. LPS then probably exerts its mitogenic activity by incorporating itself into the cell membrane. Because the lipid A/core portion of LPS bears structural resemblance to the second messenger ceramide, LPS could interact with ceramide-activated protein kinases. However, while LPS is a potent activator of human macrophages, it is not directly mitogenic for human B cells; it acts like a type 2 antigen for human B cells. For murine B cells, one can distinguish between the polyclonal B cell activator function of LPS, which occurs at a high LPS concentration, and the proper type 1 antigen function which occurs at a 1000-fold lower concentration. At the low dose, B cells with the appropriate antigen receptors have the advantage of focusing the mitogen on to themselves; the response, e.g. to DNP-haptenated LPS, then occurs only in hapten-specific B cells.

CD14 functions as a 'pattern recognition receptor" for a range of microbial constituents from gram-negative as well as gram-positive bacteria which, like LPS, activate macrophages. The B cell mitogenic properties of these substances are not yet well characterized. On the other hand, LPS reacts with a variety of receptors, including the CDllb/CD18 integrin, the animal lectin galectin-3 (expressed by activated macrophages) and others. In vivo, cytokines, inflammatory mediators and cell adhesion/cell interaction molecules from various accessory cells (macrophages, dendritic cells, natural killer (NK) cells, mast cells, activated bystander T cells, etc.) can participate in a T-independent antigen type 1 response. In vitro, high concentrations of appropriate cytokines induce all types of immunoglobulin class switches in LPS-activated B cells.

T helper cell

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