Preferential production of IgG2 antibodies by parenchymal lung B-lymphocytes during lung allograft rejection

• Published in: Transplantation proceedings Vol. 29; no. 3; pp. 1891 - 1895
• Main Authors: Wilkes, D.S., Sidner, R.A., Mathur, P.N., Niemeier, M., Schwenk, R., Heidler, K.M., Bowen, L.K.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 01.05.1997; Elsevier Science
• Subjects: Antibody Formation; Antigens, CD - analysis; Antigens, CD20 - analysis; B-Lymphocytes - immunology; B-Lymphocytes - pathology; Biological and medical sciences; Biopsy; Bronchiolitis Obliterans - immunology; Bronchiolitis Obliterans - pathology; CD4 Antigens - analysis; CD8 Antigens - analysis; Cells, Cultured; Diagnosis, Differential; Graft Rejection - immunology; Graft Rejection - pathology; Humans; Immunoglobulin G - biosynthesis; Immunoglobulin G - classification; Lung Transplantation - immunology; Lung Transplantation - pathology; Medical sciences; Postoperative Complications; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the respiratory system; Transplantation, Homologous; Human; Immunoglobulins; Immune response; Antibody; Lung; Parenchyma; Transplantation; B-Lymphocyte; IgG2; Homotransplantation; Rejection; Immunological investigation; Surgery; Humoral immunity
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/S0041-1345(97)00109-7

Lung transplantation has become an increasingly utilized modality for the treatment of various endstage pulmonary diseases. However, the lung is more prone to rejection than other solid organ allografts, likely due to the many immunocompetent cells in the donor lung. The immune mechanisms that mediate solid organ allograft rejection are believed to involve the presentation of donor alloantigens to recipient lymphocytes stimulating both cellular and humoral immunity. The cellular immune response to lung alloantigen can be due to the stimulation of either T-helper-1 type (Thl) lymphocytes which produce gamma interferon (γIFN) and interleukin (IL-2), or T-helper-2 type (Th2) lymphocytes which produce interleukins 4, 5, and 10. Investigators have demonstrated that solid organ allograft rejection was associated with upregulated Thl lymphocyte activation in vivo. Th1 and Th2 cytokines lead to the production of distinct IgG subtypes. γIFN stimulates IgG2a production in murine studies. and IgG2 production in human studies. IL-4 induces IgG1 production in murine studies. Similar to cellular immunity, humoral activity during allograft rejection has also been demonstrated to be secondary to Th1 lymphocyte activation. For example, Kupiec-Weglinski et al demonstrated that IgG alloantibody production was the result of enhanced γIFN production during cardiac allograft rejection in rats. Similarly, in a murine model of liver allograft rejection, only IgG2a antibodies were deposited in the rejecting allograft, and we reported that increased IgG2 concentrations in allograft bronchoalveolar lavage fluid (BAL) coincided with human lung allograft rejection. Other investigators have reported that the presence of large numbers of B-lymphocytes at the sites of rejection activity may be associated with a refractory response to immunosuppressive therapy, and possibly the development of obliterative bronchiolitis (0B). However, it is not known if B-lymphocytes present at the sites of rejection activity actually synthesize IgG antibodies. In addition, the source of increased IgG2 concentrations in allograft BAL fluid during rejection, ie, local production by parenchymal lung lymphocytes or passive transudation from serum, has not been evaluated. The purpose of the current study was to determine if lung allograft B-lymphocytes synthesize IgG antibodies during rejection and assess if IgG2 is preferentially produced.