Effects of progesterone on B cells and antibody secretion

SILVIA MIRANDA

Progesterone: Functions, Uses and Research Insights? (Hardcover edited collection)

Nova Science Publishers

Lugar: New York; Año: 2016; p. 1 - 17

Progesterone is synthesized in gonads, adrenal cortex, placenta and brain. The circulating levels during the female folicular phase of the menstrual cycle are similar to those seen in males. Several reports describe its immune suppressive properties on T lymphocytes, macrophages, dendritic cells (DCs) and natural killer (NK) cells. However, the effects of progesterone on B cells and antibody secretion were scarcely explored and are reviewed in this chapter. The expression of classic nuclear progesterone receptors (PR) in B-lymphocytes was reported in chicken and mouse, but they were not found in humans until now. We have demonstrated the expression of both nuclear and membrane progesterone receptors (mPR) in mouse hybridoma cells. Interestingly, progesterone was able to up-regulate the expression of both of them at high doses. Progesterone did not affect viability, cell cycle and proliferation in different B cell lines. It directly down-regulated the expression of the co-stimulatory molecules CD80 and CD86 on splenic mouse B cells thus inhibiting their activation and antigen presentation function. Importantly, progesterone inhibited the transcription of AID (activation-induced deaminase) in activated mouse splenic B cells by directly binding to the AID promoter. This progesterone-induced repression was extended to the protein level and activity on class switch recombination and somatic hypermutation, thus progesterone can interfere with affinity maturation. Progesterone did not show to modify the titer of antibodies secreted in vitro. However, we have reported that this hormone can induce changes in the glycosylation pattern of IgG which in turn might influence their physicochemical and biological properties. This occurs by means of a switch in the expression between the isoforms of the catalytic subunit (STT3-A and STT3-B) of the OST (oligosaccharyltransferase) complex, which are endowed with distinct enzymatic properties and operates in a PIBF (progesterone induced blocking factor) dependent manner. The modulation of the expression of STT3 isoforms by progesterone was also demonstrated in vivo in a mouse model. Our works also demonstrated that progesterone is able to regulate the expression and activity of two isoforms of UDP-Glucose:glycoprotein glucosyltransferase (UGGT) in a mouse hybridoma. UGGT activity was also determined in isolated B cells from peripheral blood in normal women. UGGT is a central component of the endoplasmic reticulum (ER) glycoprotein folding quality control system, which prevents the exit of misfolded proteins. In consequence, progesterone can regulate the correct folding of proteins attenuating ER stress which could lead cell to dysfunction and disease. Identifying key molecular mechanisms that link progesterone with B lymphocyte functions will explain physiological aspects of immunity as well as will allow the identification of new therapeutic targets.