The antibody response in Lyme disease.

We determined the antibody response against the Ixodes dammini spirochete in Lyme disease patients by indirect immunofluorescence and an enzyme-linked immunosorbent assay (ELISA). The specific IgM response became maximal three to six weeks after disease onset, and then declined, although titers sometimes remained elevated during later disease. Specific IgM levels correlated directly with total serum IgM. The specific IgG response, often delayed initially, was nearly always present during neuritis and arthritis, and frequently remained elevated after months of remission. Although results obtained by indirect immunofluorescence and the ELISA were similar, the ELISA was more sensitive and specific. Cross-reactive antibodies from patients with other spirochetal infections were blocked by absorption of sera with Borrelia hermsii, but titers of Lyme disease sera were also decreased. To further characterize the specificity of the humoral immune response against the I. dammini spirochete, 35S-methionine-labeled spirochetal antigens were identified by immunoprecipitation with sera from Lyme arthritis patients. These polypeptides had molecular weights of 62, 60, 47, 37, 22, 18, and 15 kDa, and were not recognized by control sera. We conclude that the ELISA, without absorption, is the best method to assay the humoral immune response in Lyme disease, and we have identified methionine-containing spirochetal polypeptides that may be important in Lyme arthritis.     

Inhibition of the immune response by membrane-bound antibody.

Cells from the spleens of "normal" swine, which were pretreated with pronase to remove surface membrane-bound immunoglobulin, gave an enhanced hemolytic plaque-forming cell response to sheep red blood cells in vitro in comparison with untreated controls. The enhancement could be abrogated by preincubating pronase-treated spleeen cells in preparations containing antibody to sheep red blood cells. This effect was demonstrated by autologous sera, immune sera, and all three known classes of porcine serum immunoglobulins, including IgM, IgA, and IgG and could be removed by absorption with sheep red blood cells. Surface membrane-bound antibody exerted its effect by binding to the nonadherent cell population. The response of normal spleen cells was unaffected by antibody treatment. Pronase-treatment was not mitogenic, did not function as a polyclonal B cell activator, and did not selectively eliminate T or B cells. The results indicate that removal of antibody from the surface of lymphoid cells enhanced the humoral immune response invitro and confirm that membrane-bound antibody can inhibit response to antigen.     

Basophil-sensitizing antibody response to herpes simplex viruses in rabbits.

Antibodies to herpes simplex virus type 1 and type 2 were detected in the sera of rabbits by release of histamine from basophils sensitized in vitro with the sera. The time course of the appearance of the antibodies, the dose-response curve of the release of histamine in relation to antigen concentration, the sedimentation characteristics of the antibodies in sucrose gradients, and the ability to destroy the sensitizing capacity of the sera with heat suggest that the antibodies being assessed were of the IgE class. These antibodies were induced in animals injected intradermally, intramuscularly, and i.p. with live virus. The antibodies were detected 1 week after primary injection and a similar time course of antibody appearance was observed after a second or third injection. The same cross-reactivity between type 1 and type 2 virus observed with IgG antibody was also observed with IgE antibody.     

Characterization of the antibody response against the type II collagen induced by anti-idiotypic antibody.

We reported that rabbit anti-idiotypic antibody (Ab2) against mAb, termed 1-5 (Ab1) and reactive with human type II collagen (CII) induced antibody response to CII in DBA/1J mice susceptible to collagen-induced arthritis. In the present study, we further characterized the anti-CII antibody response elicited by Ab2 with respect to epitope specificity, putative genetic background, and IgG subclass. Most of anti-CII antibodies (polyclonal Ab3) derived from Ab2-immunized mice were of the IgG1 subclass. We purified polyclonal Ab3, using a CII-coupled immunoadsorbent column and we developed monoclonal Ab3 from Ab2-immunized mice. Both purified polyclonal Ab3 and two monoclonal Ab3s specifically reacted with a selected epitope on CII, recognized by Ab1. The anti-CII antibody response stimulated by Ab2 was observed in DBA/1J (H-2q, Igh-1c) and DBA/2 (H-2q, Igh-1c) mice, but not in the BALB/c (H-2d, Igh-1a) and C57BL/6 (H-2b, Igh-1b) strains, thereby suggesting that the anti-CII antibody response elicited by Ab2 is controlled by the Igh gene.     

Mathematical models of antibody response

An antigen triggers the clonal expansion of B lymphocytes accompanied by antibody production. This paper presents and compares the basic ideas of three mathematical models of B cell differentiation and proliferation.     

Regulation of antibody response in vitro. X. Biphasic effect of cyclic AMP on the secondary anti-hapten antibody response to anti-immunoglobulin and enhancing soluble factor.

The effect of elevation of an intracellular cyclic AMP level on in vitro anti-hapten antibody response was studied, by using mesenteric lymph node cells of rabbits which were primed with dinitrophenylated Ascaris antigen (DNP-Asc) or DNP-ragweed antigen (DNP-Rag). The anti-hapten antibody response was induced by stimulation of the primed B cells by either DNP-heterologous carrier conjugate or anti-immunoglobulin (anti-Ig) for 24 hr (first stage), followed by 6-day culture of the activated cells in the presence of nonspecific enhancing factor (second stage). The stimulation with anti-Ig induced IgG anti-hapten antibody response and enhanced the formation of total IgG. Addition of dibutyryl cyclic AMP or aminophylline with anti-Ig or DNP-heterologous carrier during the first stage enhanced IgG anti-hapten antibody response. The optimal concentration of these reagents for the enhancement was 5 x 10(-4) M to 10(-3) M. The presence of 5 x 10(-6) M prostaglandin E1 during the first stage also enhanced the antibody response. Similarly, the presence of dibutyryl cyclic AMP or aminophylline during the stimulation of DNP-Rag-primed cells with homologous antigen (first stage) enhanced the antibody response. If the same concentration of dibutyryl cyclic AMP or aminophylline was added together with enhancing soluble factor during the second stage after the stimulation of the primed cells with anti-Ig, both the antibody response and the formation of IgG were suppressed. The antibody response of DNP-Rag-primed cells stimulated with homologous antigen was also suppressed if dibutyryl cyclic AMP or aminophylline was added during the subsequent culture (second stage). Evidence was obtained that suppression of antibody response by cyclic AMP during the second stage is probably due to inhibition of the proliferation of B cells. Neither of these drugs suppressed the formation of enhancing soluble factor from the carrier-specific cells stimulated with the homologous carrier. The results obtained in the present experiments suggested that stimulation of hapten-primed B cells with anti-gamma chain in the presence of an optimal concentration of dibutyryl cyclic AMP resulted in the formation of a significant amount of IgG anti-DNP antibody without participation of T cells.     

In vitro antibody response to influenza virus. I. T cell dependence of secondary response to hemagglutinin.

A good secondary IgG response to the hemagglutinin (HA) of influenza virus has been obtained in vitro in Marbrook-type cultures of influenza-primed mouse spleen cell suspensions stimulated with inactivated influenza virus. Anti-HA antibody was quantitated by a solid phase radioimmunoassay (RIA) by using purified HA as substrate. The T dependence of this secondary response was shown by depletion of T cells and reconstitution with a source of primed or unprimed T cells. The help given by T cells primed to the homologous virus was many times greater than that given by unprimed T cells, although the latter was significant. The system described will allow investigation of the specificity requirements of helper T cells engaged in the anti-HA response.     

Production of auto-anti-idiotypic antibody during the normal immune response. VIII. Effect of auto-anti-idiotypic antibody on contact sensitivity

An eluate prepared by brief incubation of spleen cells from 2,4,6-trinitrophenyl (TNP) lysyl-Ficoll immunized mice with TNP-epsilon-amino-n-caproic acid causes a specific inhibition of the induction of contact sensitivity by 2,4,6-trinitrochlorobenzene skin painting. The active factor in the eluate binds to an anti-mouse immunoglobulin (Ig) immunoadsorbent column but not to a TNP immunoadsorbent column and is therefore Ig but not anti-TNP antibody. The active factor does bind to an immunoadsorbent prepared from anti-TNP antibody, suggesting that the factor has anti-idiotype specificity. Evidence based upon hapten-reversible inhibition of plaque formation and an enzyme-linked immunosorbent assay (ELISA) indicates that the eluates contain auto-anti-idiotype antibody specific for anti-TNP antibody. It is suggested that auto-anti-idiotype antibody spontaneously produced during the immune response to a T-independent antigen can specifically downregulate contact sensitization to the same epitope.