Enhanced Immunoglobulin Formation of Immortalized B Cells From Hypertensive Patients

Abstract

Increased immunoglobulin levels and leukocyte counts have frequently been reported in essential hypertension. The underlying mechanisms, however, have remained obscure. Enhanced Na(+)-H+ exchanger activity is another frequently observed abnormality in essential hypertension that persists in immortalized B lymphoblasts and coincides with enhanced proliferation. We investigated the capacity of B lymphoblasts from essential hypertensive patients to synthesize and secrete immunoglobulins. Six B cell lines from essential hypertensive patients with enhanced Na(+)-H+ exchanger phenotype and six cell lines from normotensive subjects were studied. Lymphocyte markers were visualized by immunostaining. Immunoglobulin secretion was analyzed by enzyme-linked immunosorbent assay. These cell lines did not differ with respect to B cell markers. In response to 100 nmol/L platelet-activating factor, cells from hypertensive patients proliferated distinctly more quickly and their cell number increased by 3.9 +/- 0.4-fold (mean +/- SD) within 4 days, whereas the number of cells from normotensive subjects increased by only 2.6 +/- 0.1-fold. Furthermore, platelet-activating factor induced average increases in IgM and IgG formation of 13.3- and 5.4-fold, respectively, in lymphoblasts from hypertensive patients, which was significantly higher than increases in cells from normotensive subjects (1.4- and 1.2-fold, respectively). Thus, lymphoblasts from hypertensive patients proliferate more quickly and secrete more immunoglobulins in response to a physiological stimulus in vitro. This may contribute to the raised immunoglobulin levels and leukocyte counts reported in vivo.

Glucocorticoid modulation of Ca2+ homeostasis in human B lymphoblasts

“…Statistical analyses of the rate constants derived from curve-fitting the Mn¥ data were performed using weighted least squares according to the method described by Johnson & Milliken (1983 To examine Cafl signalling in LCLs, we used plateletactivating factor (PAF), a potent cytokine that has diverse actions throughout the immune system (Snyder, 1990). In B cells, this lipid mediator alters several immunomodulatory functions including nuclear-factor-ê Bmediated immunoglobulin synthesis and secretion (Smith & Schearer, 1994;Rosskopf et al 1995), cytokine expression (e.g. TNFá and IL-2; and Ca¥-dependent expression of cell cycle genes and proliferation (Mazer et al 1991(Mazer et al , 1994Rosskopf et al 1995).…”

“…In B cells, this lipid mediator alters several immunomodulatory functions including nuclear-factor-ê Bmediated immunoglobulin synthesis and secretion (Smith & Schearer, 1994;Rosskopf et al 1995), cytokine expression (e.g. TNFá and IL-2; and Ca¥-dependent expression of cell cycle genes and proliferation (Mazer et al 1991(Mazer et al , 1994Rosskopf et al 1995). The PAF receptor is expressed in both resting and activated cells (Nguer et al 1992(Nguer et al , 1996; its activation results in phosphatidylinositol bisphosphate hydrolysis, IP× generation and a transient Cafl response (Mazer et al 1991).…”

Platelet-activating Factor and Normal or Leukaemic Haematopoiesis

“…PAF has no effect on the proliferation of several human myeloma cell lines [53] and its enhancing effect on the proliferation of Raji lymphoblasts is controversial [66,67]. By contrast, it enhances the growth of immortalised B cells from hypertensive patients [68] but not those of tonsillar B lymphocytes [56]. Finally, while PAF has no effect on the spontaneous proliferation of peripheral human B lymphocytes, it affects their PMA-or IgM-stimulated growth [55].…”

G Proteins, Hypertension, and Coronary Heart Disease -Novel Findings and Hypotheses

“…77] left ventricular hypertrophy [69] increased while blood cell count [78][79][80] Increased formation of immunoglobulins [75] increased concentration o f immuno globulins in vivo [81][82][83] cally disadvantageous clinical parameter [65,66]. It has re mained enigmatic w hy this phenomenon does not develop in all patients despite similar blood pressure elevation and duration o f hypertension.…”