Wasp Venom Rush Immunotherapy Induces Transient Downregulation of B Cell Surface Molecule Expression

Background: Little is known about the involvement of B cells in venom immunotherapy (VIT). To elucidate changes in the B cell phenotype during this process, we examined the expression of several surface molecules on peripheral B cells before and during VIT. Methods: 15 venom-allergic patients with a history of systemic reactions after a wasp sting and venom-specific skin test reactivity as well as serum IgE were investigated before VIT (day 1), 1 day after reaching a maintenance dose of 100 µg (day 6) during inpatient rush VIT, and again on day 26 during continued outpatient maintenance therapy. Changes in the serum levels of total IgE, allergen-specific IgE (sIgE) and sIgG4 were measured by ELISA. Expression of several surface molecules on double-labelled B cells was studied by flow cytometry of peripheral blood mononuclear cells. Results: Levels of total IgE, sIgE and sIgG4 showed a significant increase after 26 days of VIT. On day 6, cell surface expression of HLA- II-DR, CD5, CD32 and CD54 was decreased in intensity and numbers of positive cells compared to day 1, while on day 26, expression of these molecules approached again baseline levels. Furthermore, a trend to decreased CD23 was noted on day 6. No changes were observed for CD40, CD86, CD95 and HLA-I-ABC. Conclusion: These data show that during initiation of rush VIT, B cell expression of surface molecules involved in T-B cell cooperation and antigen presentation is downmodulated. B cells may thus be additional direct or indirect targets of high-dose antigen therapy and contribute to the persistence of TH1 responses during maintenance VIT treatment.

[1]  A. V. D. Stolpe,et al.  Intercellular adhesion molecule-1 , 2020, Journal of Molecular Medicine.

[2]  P. Bruhns,et al.  The Pseudo-immunoreceptor Tyrosine-based Activation Motif of CD5 Mediates Its Inhibitory Action on B-cell Receptor Signaling* , 2000, The Journal of Biological Chemistry.

[3]  S. Bondada,et al.  Negative regulation of antigen receptor‐mediated signaling by constitutive asociation of CD5 with the SHP‐1 protein tyrosine phosphatase in B‐1 B cells , 1999, European journal of immunology.

[4]  P. Youinou,et al.  CD5 expression in human B-cell populations. , 1999, Immunology today.

[5]  C. Akdis,et al.  IL‐10‐induced anergy in peripheral T cell and reactivation by microenvironmental cytokines: two key steps in specific immunotherapy , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[6]  I. Bellinghausen,et al.  Decreased release of histamine and sulfidoleukotrienes by human peripheral blood leukocytes after wasp venom immunotherapy is partially due to induction of IL-10 and IFN-gamma production of T cells. , 1999, The Journal of allergy and clinical immunology.

[7]  C. Akdis,et al.  Determinants and Mechanisms of Human Immune Responses to Bee Venom Phospholipase A2 , 1998, International Archives of Allergy and Immunology.

[8]  Williams,et al.  Inhibition of sCD23 and immunoglobulin E release from human B cells by a metalloproteinase inhibitor, GI 129471 , 1998, Immunology.

[9]  Venge,et al.  Activation of B‐lymphocytes during pollen season. Effect of immunotherapy , 1998, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[10]  C. Akdis,et al.  Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase A2 induces specific T-cell anergy in patients allergic to bee venom. , 1998, The Journal of allergy and clinical immunology.

[11]  M. Kowalski,et al.  Mechanisms of specific immunotherapy of allergic diseases , 1998, Allergy.

[12]  R. Geha,et al.  Molecular Mechanisms of Immunoglobulin E Regulation , 1998, International Archives of Allergy and Immunology.

[13]  Andreas Radbruch,et al.  Systemic T‐cell unresponsiveness during rush bee‐venom immunotherapy , 1998, Allergy.

[14]  C. Akdis,et al.  Differential regulation of human T cell cytokine patterns and IgE and IgG4 responses by conformational antigen variants , 1998, European journal of immunology.

[15]  J. Bonnefoy,et al.  CD86 (B7-2) on Human B Cells , 1997, The Journal of Biological Chemistry.

[16]  A. Enk,et al.  Insect venom immunotherapy induces interleukin‐10 production and a Th2‐to‐Th1 shift, and changes surface marker expression in venom‐allergic subjects , 1997, European journal of immunology.

[17]  J. Bonnefoy,et al.  Structure and functions of CD23. , 1997, International reviews of immunology.

[18]  G. Nossal Clonal anergy of B cells: a flexible, reversible, and quantitative concept , 1996, The Journal of experimental medicine.

[19]  M. Joseph,et al.  Venom immunotherapy modulates interleukin‐4 and interferon‐γ messenger RNA expression of peripheral T lymphocytes , 1996, Immunology.

[20]  H. Ochi,et al.  B cell‐B cell interaction through intercellular adhesion molecule‐1 and lymphocyte functional antigen‐1 regulates immunoglobulin E synthesis by B cells stimulated with interleukin‐4 and anti‐CD40 antibody , 1996, European journal of immunology.

[21]  W. Fridman,et al.  The same tyrosine-based inhibition motif, in the intracytoplasmic domain of Fc gamma RIIB, regulates negatively BCR-, TCR-, and FcR-dependent cell activation. , 1995, Immunity.

[22]  H. Quill,et al.  Altered CD40 ligand induction in tolerant T lymphocytes , 1995, European journal of immunology.

[23]  M. Jutel,et al.  Bee venom immunotherapy results in decrease of IL-4 and IL-5 and increase of IFN-gamma secretion in specific allergen-stimulated T cell cultures. , 1995, Journal of immunology.

[24]  T. Kipps,et al.  Tumor necrosis factor-alpha facilitates induction of CD80 (B7-1) and CD54 on human B cells by activated T cells: complex regulation by IL-4, IL-10, and CD40L. , 1995, Cellular immunology.

[25]  D. Umetsu,et al.  Interleukin 4 production by CD4+ T cells from allergic individuals is modulated by antigen concentration and antigen-presenting cell type , 1995, The Journal of experimental medicine.

[26]  J. Ring,et al.  A reduction in allergen-induced Fc epsilon R2/CD23 expression on peripheral B cells correlates with successful hyposensitization in grass pollinosis. , 1995, The Journal of allergy and clinical immunology.

[27]  J. Bonnefoy,et al.  CD21 is a ligand for CD23 and regulates IgE production , 1992, Nature.

[28]  H. Wortis,et al.  Treatment of murine CD5- B cells with anti-Ig, but not LPS, induces surface CD5: two B-cell activation pathways. , 1991, International immunology.

[29]  D. Richards,et al.  Sub‐class of IgG anti‐bee venom antibody produced during bee venom immunotherapy and its relationship to long‐term protection from bee stings and following termination of venom immunotherapy , 1986, Clinical allergy.

[30]  H. Malling,et al.  The IgE and IgG subclass antibody response in patients allergic to yellow jacket venom undergoing different regimens of venom immunotherapy. , 1985, The Journal of allergy and clinical immunology.