We studied B-lymphocyte function in 12 homosexual male patients with the acquired immunodeficiency syndrome, 5 healthy homosexual men, and 12 heterosexual controls. In comparison with the heterosexual controls, the patients were found to have elevated numbers of cells spontaneously secreting immunoglobulin, decreased B-cell proliferative responses to T-cell-independent B-cell mitogens, and qualitatively deficient helper T cells. The hyperactive spontaneous B-cell responses as well as the refractoriness to signals for T-cell-independent B-cell activation were highly suggestive of an in vivo polyclonal activation of B cells and may have been responsible for the manifestations of B-cell hyperreactivity, such as hypergammaglobulinemia, seen in these patients. We conclude that the scope of immune dysfunction in the acquired immunodeficiency syndrome involves B cells as well as T cells.

We studied purified subpopulations of lymphocytes from patients with the acquired immunodeficiency syndrome (AIDS) in order to determine whether intrinsic defects in lymphocyte function, aside from those due to alterations in lymphocyte numbers, were present. Mitogen-stimulated DNA synthesis, production of gamma interferon, production of interleukin-2, and expression of interleukin-2 receptors, although variably decreased in unseparated cell populations, were normal in populations of purified T-cell subsets. In contrast, DNA synthesis in response to the soluble protein antigen tetanus toxoid was decreased in both unseparated and purified T-cell subpopulations. Cell-mixing experiments demonstrated that the hyporesponsiveness of the unfractionated lymphocytes from patients with AIDS was not due to active suppression. We conclude that the lymphocytes of patients with AIDS, although capable of undergoing a normal degree of blast transformation and lymphokine production after mitogenic stimulation, have an intrinsic defect in their ability to recognize and respond to soluble antigen.

Background: The mechanism(s) of nociceptive dysfunction and potential roles of opioid neurotransmitters are unresolved in the chronic pain syndromes of fibromyalgia and chronic low back pain.

Previous studies have identified stress system dysregulation in fibromyalgia (FM) patients; such dysregulation may be involved in the generation and/or maintenance of pain and other symptoms. Corticotropin-releasing factor (CRF) is the principal known central nervous system mediator of the stress response; however, to date no studies have examined cerebrospinal fluid (CSF) CRF levels in patients with FM. The relationship between CSF CRF level, heart rate variability (HRV), and pain, fatigue, and depressive symptoms was examined in patients with FM. Among participants (n ¼ 26), CSF CRF levels were associated with sensory pain symptoms (r ¼ 0.574, p ¼ 0.003) and affective pain symptoms (r ¼ 0.497, p ¼ 0.011), but not fatigue symptoms. Increased HRV was also strongly associated with increased CSF CRF and FM pain. In multivariate analyses adjusting for age, sex, and depressive symptoms, the association between CSF CRF and sensory pain symptoms (t ¼ 2.54, p ¼ 0.027) persisted. Women with FM who reported a history of physical or sexual abuse had lower CSF CRF levels than women who did not report such a history. CSF CRF levels are associated with both pain symptoms and variation in autonomic function in FM. Differences in CSF CRF levels among women with and without a self-reported history of physical or sexual abuse suggest that subgroups of FM patients may exist with different neurobiological characteristics. Further studies are needed to better understand the nature of the association between CSF CRF and pain symptoms in FM.

The present study demonstrates the graded effect of in vitro corticosteroids (CSs) on

The immune function of B lymphocytes from 12 patients with nonneoplastic immune-mediated diseases receiving chronic lowdose (2 mg/kg per d) cyclophosphamide (CY) was evaluated. There was a selective and differential suppressive effect of CY therapy on the various stages of the B cell cycle including activation, proliferation, and differentiation. The proliferative responses to Staphylococcus aureus Cowan strain I (SAC) and mitogenic concentrations of anti-p were suppressed. In contrast, B cells that have been presumably activated in vivo proliferated with a normal pattern when exposed to B cell growth factor in vitro. Chronic low-dose CY therapy also suppressed B cell differentiation. Secretion of immunoglobulin by B cells following in vitro triggering with SAC and a T cell supernatant was suppressed in CY-treated patients. Moreover, differentiation of the large in vivo-activated B cells (which do not require an in vitro activation signal) in the presence of appropriate T lymphocyte supernatant was also suppressed. This selective suppression of B cell function at multiple points in the B cell cycle may be responsible for the efficacy of CY therapy in certain antibody and immune complex-mediated diseases.

The availability of an antigen-induced, antigen-specific system to measure in vitro antibody responses by human B cells is critical for the precise delineation of the physiology of human B cell activation and immunoregulation. Specific antibody production has been studied in man for several years. However, in doing so, some of the systems that have been employed have required induction by polyclonal B cell activators, whereas others, which have utilized direct stimulation by antigen, have been technically difficult to perform or unpredictable in terms of individual responses (1-3).We have previously reported (4) that the unfractionated peripheral blood mononuclear cells from normal human subjects immunized to the soluble protein antigen keyhole limpet hemocyanin (KLH) 1 could be induced in vitro by antigen alone or by pokeweed mitogen (PWM) to produce specific antibody. In each case, the specific antibody production was nonetheless associated with polyclonal activation. In the present study, we have characterized the overlap between antigen specificity and polyclonality in the induction and expression of antigen-induced antibody production and have demonstrated a dichotomy between antigen-specific and polyclonal responses to two distinct protein antigens, KLH and tetanus toxoid (TT). In addition, we have precisely defined the culture conditions and cellular requirements for antigeninduced, antigen-specific antibody production by human peripheral blood B cells. Materials and MethodsImmunizations. Normal subjects, aged 18-40 yr, received two subcutaneous injections of 5 mg KLH (Calbiochem-Behring Corp., American Hoechst Corp., La Jolla, Calif.), which had been dialyzed against phosphate-buffered saline (PBS) and passed through a 0.45-/~m millipore filter. Injections were spaced by 2 wk. TT (Wyeth Laboratories, Marietta, Pa.), 5 If, was also administered subcutaneously to some subjects. Immunizations were carried out under peerreviewed National Institutes of Health protocols.Cell Separations. Peripheral blood mononuclear cells were obtained from Hypaque-Ficoll gradients in a standard fashion (5). These unfractionated mononuclear cells were 10-30% monocytes, 70-90% lymphoeytes, and 0-5% basophils and granulocytes by morphology and x Abbreviations used in this paper." KLH, keyhole limpet hemocyanin; PBS, phosphate-buffered saline; PWM, pokeweed mitogen; TT, tetanus toxoid.

No abstract