Suppression of human B lymphocyte function by cyclophosphamide.

Abstract

The immune responses of 16 patients with nonneoplastic immune mediated diseases including Wegener's granulomatosis, systemic necrotizing vasculitis, cutaneous vasculitis, and relapsing nodular panniculitis were evaluated before and during therapy with chronic low-dose (2 mg/kg/day) cyclophosphamide. A striking selective suppression of B cell function was noted as measured by PWM-induced immunoglobulin secretion. This suppression was a direct effect on the B cells themselves because T cell function, measured by blastogenic responses to the mitogens PHA, Con A, and PWM, was not significantly suppressed. Furthermore, the ability of T cells from cyclophosphamide-treated patients to provide helper function in T cell-dependent B cell assays remained intact. Treated patients manifested a total lymphocytopenia without a selective depletion of relative proportions of B cells or T cell subsets. However, the spontaneous secretion of immunoglobulin by peripheral blood B cells that is elevated in untreated patients was suppressed back to normal levels during cyclophosphamide therapy. This selective effect on spontaneous and induced secretion of immunoglobulin by human B cells may help explain the efficacy of cyclophosphamide therapy in certain antibody and immune complex-mediated diseases.

Response of Chronic, Relapsing Wegener's Granulomatosis with Severe Pulmonary Involvement to Anti-CD20 Monoclonal Antibody (Rituximab)

“…This alkylating agent remains the most effective drug for the control of disease activity. It targets all types of proliferating immune cells nonspecifically, influencing cell-mediated and humoral immune response [6]. It has most profound effect on B cells function and stronger suppressive effect on CD8+ T cells than CD4+ T lymphocytes.…”

“…Cambridge et al suggested that total immunoglobulins are produced by long-lived plasma cells, which do not express the CD20 antigen and are not affected by anti-CD20 monoclonal antibody [21]. Several groups of investigators suggest that the pathogenic role of Blymphocytes in Wegener's granulomatosis goes beyond their function for autoantibody production [6,19].…”

“…Initial studies implicating B lymphocytes as active participants in the pathogenesis of WG provided the rationale for using Cyclophosphamide to treat this disease [6,7]. More recently, the number of activated peripheral blood B lymphocytes has been linked to disease activity and to extent of organ involvement [8].…”

Clinical Development and Perspectives of CIMAvax EGF, Cuban Vaccine for Non-small-cell Lung Cancer Therapy

“…[35][36][37][38][39] En este contexto, se consideró hipotéticamente que los clones linfocitarios potencialmente autoreactivos, capaces de generar una respuesta de Acs contra EGF autólogo, reemergen de la depleción máxima de linfocitos inducida por la quimioterapia (nadir de linfopenia), ampli¿ cados con ventaja homeostática. [40,41] Sobre la base de estos conceptos y los resultados de las investigaciones preclínicas, se propuso un esquema terapéutico combinando vacuna, quimioterapia y más vacuna (VQV). Este Original Scienti¿ c Articles esquema se evaluó en el quinto ensayo clínico fase I/II (Piloto 5), comenzado en 2001 en el Hospital Hermanos Ameijeiras (HHA) de la Habana, utilizándose la formulación CIMAvax EGF (EGF/ P64k/Montanide ISA 51) en 20 pacientes con CPCNP estadios IIIB/IV.…”

Myeloablative autologous haematopoietic stem cell transplantation resets the B cell repertoire to a more naïve state in patients with systemic sclerosis

“…CYC depletes certain populations of T cells 22 and suppresses B cells. 23 Additionally, CYC is immunosuppressive by virtue of toxicity to lymphocytes, with less impact on haematopoietic stem cells (HSCs). In contrast, myeloablative autologous HSCT treatment depletes both lymphocytes and HSCs by total body irradiation, with reconstitution of these population through CD34-selected HSC autograft.…”