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P McFarland

Publications and source records attributed to P McFarland.

8 recordsLinked to original sources
PubMed1991

Intracellular signaling events associated with the induction of proliferation of normal human B lymphocytes by two different antigenically related human B cell growth factors (high molecular weight B cell growth factor (HMW-BCGF) and the complement factor Bb).

High molecular weight B cell growth factor (HMW-BCGF) and the complement component, Factor B, are antigenically related. HMW-BCGF and the physiologic Factor B activation fragment Bb, are both mitogenic for B lymphocytes and compete for binding to the B cell plasma membrane (Peters, M., Ambrus, J. L., Jr., Fauci, A., and Brown, E. (1988) J. Exp. Med. 168, 1225-1235). To understand which second messengers that occur after ligand-receptor interaction are associated with mitogenesis, we have examined the early signaling events after stimulation of activated B cells with these related growth factors. HMW-BCGF but not Bb increased [cAMP]i with a maximum between 45 and 60 min after stimulation. The increase in [cAMP]i was inhibited by indomethacin, suggesting that prostaglandin synthesis is involved in this response. Increase in [cAMP]i induced by HMW-BCGF, cholera toxin, or dibutyryl cAMP was associated with increased expression of the HMW-BCGF receptor, but there was no increase in proliferation of activated B cells when they were stimulated with cAMP agonists other than HMW-BCGF. These data suggest that cAMP is associated with regulation of receptor expression but is neither necessary nor sufficient for induction of proliferation. Both HMW-BCGF and Bb increased cellular levels of diacylglycerol and a water-soluble molecule which could be labeled with both [3H]myoinositol and [14C] glucosamine. However, only HMW-BCGF induced increases in intracellular calcium. Thus, two antigenically related B cell growth factors, HMW-BCGF and Bb, produce overlapping but distinct sets of second messengers after incubation with Sac-activated B cells. Since both induced increases in diacylglycerol and water-soluble inositol, one or both of these molecules may be involved in the proliferative signal generated by the related growth factors. In contrast, the increase in [cAMP]i caused by HMW-BCGF but not Bb is involved in the signal to increase HMW-BCGF receptor expression, but is unrelated to proliferation.

B-Lymphocytes↗
PubMed1991

Induction of proliferation by high molecular weight B cell growth factor or low molecular weight B cell growth factor is associated with increases in intracellular calcium in different subpopulations of human B lymphocytes.

The activation of resting B cells with anti-surface Ig is associated with transient increases in intracellular calcium. In the present study, we demonstrate that stimulation of B cells which have already been activated by Staphylococcus aureus Cowan I (Sac), with high molecular weight B cell growth factor (HMW-BCGF) or low molecular weight B cell growth factor (LMW-BCGF), but not IL-2, IL-4, or interferon-gamma, is associated with an increase in intracellular calcium, which is modest compared to that seen with anti-Ig (approximately 100 nM vs approximately 400 nM). The increases in intracellular calcium induced by HMW-BCGF or LMW-BCGF occur in distinct but overlapping subpopulations of B cells. Thus, increases in intracellular calcium in human B cells occur not only upon activation but also upon the induction of proliferation by certain (but not all) B cell growth factors. Presumably, the effect of increasing intracellular calcium during the induction of proliferation is to modify a different group of intracellular molecules than those induced during activation.

B-Lymphocyte Subsets↗
PubMed1991

Improved in vitro antigen-specific antibody synthesis in two patients with common variable immunodeficiency taking an oral cyclooxygenase and lipoxygenase inhibitor (ketoprofen).

In the process of performing a previously published study examining B cell function in 16 patients with common variable immunodeficiency (CVI)(J Allergy Clin Immunol 1991; 87:1138-49), we noted improved in vitro antibody (Ab) synthesis in a patient, H. B., while he was taking a cyclooxygenase and lipoxygenase inhibitor, ketoprofen. Addition of ketoprofen in vitro to B cells from patients with CVI resulted in improved proliferation and differentiation in four of five additional patients with CVI studied. One patient, besides H. B., M. K. B., whose B cells secreted increased amounts of antigen (Ag)-specific Ab in response to in vitro ketoprofen, underwent a trial of oral ketoprofen M. K. B., like H. B., demonstrated improved in vitro Ag-specific Ab production while she was taking oral ketoprofen. No increase in serum Ab levels was noted in either patient taking ketoprofen, but both patients remained infection free during the time of their ketoprofen trials (H. B., 9 months, and M. K. B., 36 months). No improvement in in vitro Ag-specific Ab synthesis was noted when H. B. and M. K. B. took oral cyclooxygenase inhibitors (naproxen or ibuprofen). Thus, additional study is warranted to examine the role of lipoxygenase products of arachidonic acid in the B cell dysfunction of CVI.

Administration, Oral↗
PubMed1991

Abnormal response to a human B cell growth factor in patients with common variable immunodeficiency (CVI).

Patients with common variable immunodeficiency (CVI) generally fail to produce antigen-specific IgG. We have identified a lymphokine called high molecular weight B cell growth factor (HMW BCGF) that expands an IgG-producing subpopulation of B cells. The B cells from 15 of 16 patients with CVI evaluated in this study failed to proliferate to HMW BCGF, although they proliferated normally to another BCGF, low molecular weight BCGF (LMW BCGF). Nevertheless, 11 patients had more than normal numbers of B cells expressing HMW BCGF receptors. The HMW BCGF receptors on the B cells of three patients with CVI studied were the same molecular weight as the normal HMW BCGF receptor. Examination of B cells from four patients with CVI for intracellular signals produced in normal B cells after stimulation with HMW BCGF revealed that B cells from patients with CVI failed to developed significant increases in cyclic adenosine monophosphate or phosphoinositides after HMW BCGF stimulation. However, cytoplasmic phosphoinositides in the B cells from all four patients with CVI were already increased above what is observed in normal B cells before stimulation with HMW BCGF (either freshly isolated or Staphylococcus aureus Cowan I-activated B cell). Thus, the failure of B cells from patients with CVI to respond to HMW BCGF may be related to their abnormal activation in vivo. Since HMW BCGF expands a subpopulation of memory B cells, the inability of CVI B cells to respond to HMW BCGF may contribute to their abnormal secondary responses to antigens.

Adolescent↗
PubMed1990

Functional studies examining the subpopulation of human B lymphocytes responding to high molecular weight B cell growth factor.

Mature human B lymphocytes perform many functions including antibody secretion, Ag presentation, preservation of memory for Ag, and lymphokine secretion. Individual resting B cells receive multiple sequential signals that determine the function(s) that will be performed by those cells. Activation signals such as Ag or Staphylococcus aureus Cowan I (Sac) stimulate overlapping but different subpopulations of B cells. After activation, B cells may be induced to proliferate by a variety of B cell growth factors (BCGF) including IL-2, IL-4, TNF-alpha, low molecular weight BCGF (LMW-BCGF), and high molecular weight BCGF (HMW-BCGF). Little information exists to explain why so many different BCGFs are involved with human B cell proliferation. The current studies were designed to examine the role HMW-BCGF plays in selecting B cells for particular functions. HMW-BCGF but not LMW-BCGF was found to inhibit Ig secretion when it was included in culture with Sac-activated B cells and B cell differentiation factors (BCDFs) including IL-6. Sorting resting B lymphocytes into surface IgD+ and IgD- populations and then stimulating each population with anti-mu revealed that the cells most responsive to HMW-BCGF resided in the surface IgD- sorted population. Sorting activated B lymphocytes into BA5 (HMW-BCGFR)+ and BA5- populations revealed that BA5+ B cells stimulated with BCDF (in the absence of HMW-BCGF) produced predominantly IgG, whereas the BA5- population produced both IgG and IgM. Finally, expansion of peripheral B cells from tetanus toxoid-immunized donors with either HMW-BCGF or LMW-BCGF revealed that the HMW-BCGF-expanded population produced predominantly IgG tetanus-specific antibody in the presence of BCDF (in the absence of HMW-BCGF), whereas the LMW-BCGF-expanded population produced IgM much greater than IgG tetanus-specific antibody. Thus, HMW-BCGF may function to expand a subpopulation of B cells for memory B cell functions.

B-Lymphocyte Subsets↗
PubMed1988

Identification of a receptor for high molecular weight human B cell growth factor.

Regulation of the proliferation of human B lymphocytes is under the control of several different signals. Various B cell growth factors (BCGF) have been described including a 60-kDa BCGF called high m.w. BCGF (HMW-BCGF). In this paper we describe a mAb BA5 that blocks the proliferation of normal activated human B lymphocytes in response to HMW-BCGF and does not affect the proliferation of T cells in response to PHA or IL-2. BA5 shows minimum binding to resting B cells, significantly enhanced binding to resting B cells, significantly enhanced binding to activated B cells and essentially no binding to resting or activated T cells. BA5 recognizes a 90-kDa protein from solubilized membranes of activated B cells. 125I-HMW-BCGF cross-linked to its binding site on activated B cells produces a 150-kDa R-protein complex. Unlabeled HMW-BCGF cross-linked to its binding site on activated B cells produces a 150-kDa band recognized by both BA5 and BCGF/1/C2 (a mAb to HMW-BCGF) using Western blotting. Thus, BA5 recognizes a molecule intimately associated with the receptor for HMW-BCGF which includes a binding site for HMW-BCGF. BA5 can be used to explore the role of HMW-BCGF and B cell proliferation in various aspects of human B cell physiology.

Animals↗
PubMed1975

Single image pericardial effusion evaluation with technetium compounds.

Three cases of suspected pericardial effusion were evaluated with rapid, noninvasive procedure, combined use of macroaggregated albumin technetium 99m and human serum albumin technetium 99m to produce a single radiography showing the heart, liver, and lung perfusion simultaneously. This technic confirmed the diagnosis of pericardial effusion in two cases and ruled out this possibility in the third case.

Adult↗