Antiidiotypic antibodies against anti-cGMP polyclonal antibodies.

Affinity-purified polyclonal anti-cGMP antibodies were obtained from rabbit serum after immunization by succinyl derivative of cGMP coupled to bovine serum albumin. These antibodies were used to raise antiidiotypic antibodies in rats. Putative antiidiotypic serum inhibited the binding of [3H]cGMP to affinity-purified anti-cGMP antibodies. The influence of immunoglobulins isolated from antiidiotypic serum on the ion conductance of rod outer segment plasma membrane fragments from frog retina was studied in patch-clamp experiments. These immunoglobulins increased the conductance of ion channels acting like a natural agonist (cGMP). Preimmune immunoglobulins did not act. The data obtained suggest that antiidiotypic antibodies interact with regulatory cGMP-binding sites of the plasma membrane channels.     

Phage-specific antibodies

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Silent antibodies

Over the past years, progress has been made in understanding B cells and antibody recognition functions, particularly in the context of autoimmune diseases. In addition to the existence of "natural antibodies", recent studies suggest the existence of immunoglobulins with no apparent specificity that may acquire polyreactivity following a mild denaturation in inflammatory sites. They are called "silent antibodies". Together with related observations on B cell development, selection and signaling, the recent insights are providing clues into our understanding of autoimmunity.     

Monoclonal antibodies

The hybridoma technology developed by K?hler and Milstein has initiated a new era in biological sciences. In the last decade the possibility of generating limited amounts of monoclonal antibodies of predefined specificity has become a routine method in many laboratories throughout the world. The constant quality of various antibody preparations from 1 hybridoma cell line represents another important advantage of this method. Apart from the use for several purposes, e.g. HLA-typing, differentiation of lymphocyte subpopulations and blood group antigens, monoclonal antibodies play an important role in the determination of various tumor markers. In most modern immunoassays monoclonal antibodies are used. Furthermore, there is nowadays a limited experience concerning the in vivo use of monoclonal antibodies in malignant disease. Radiolabelled antibody immunodetection has been applied e.g. in colorectal and testicular tumors for the detection of tumor metastases. The therapeutic use of monoclonal antibodies has been reported in some patients with tumors of the hemopoietic system. The production of new murine and human monoclonal antibodies against various tumor types is subject of current investigations. The aim of these efforts is the development of monoclonal antibodies suitable for in vitro tumor diagnosis and application in vivo.     

Catalytic antibodies

More than 10 years have now elapsed since the first reports confirmed that antibodies could be programmed as catalysts for chemical processes. Much of the initial research focussed on exploring the scope and utility of these new biocatalysts. Recently however, increasing information gleaned from X-ray analyses is allowing an exciting insight into the structural basis of antibody catalyzed reactions. This review details the evolving knowledge of the structure-function relationship for catalytic antibodies that accelerate a range of different reaction classes.     

Pathogenic antibodies in systemic lupus erythematosus: anti-LAMP antibodies

We recently demonstrated that a monoclonal anti-DNA antibody, spontaneously produced in lupus B/W mice, recognizes the same protein(s) at the surface of several human cell types involved in lupus pathogenesis including normal human erythrocytes, normal platelets and rat neuronal tissue. This cell-surface protein(s) cross-react(s) with double-stranded DNA. We suggest to call this protein(s) LAMP [lupus associated membrane protein(s)]. Here we show that: immunoglobulins eluted from kidneys of autoimmune MRL/lpr/lpr mice strongly react with LAMP. Anti-LAMP antibodies are present in large amount in MRL/lpr and B/W mice sera. Anti-LAMP are present in 25 out of 25 human SLE sera ranged as SLE on the basis of revised American Rheumatism Associated classification. Interestingly, two of these sera did not display anti DNA anti-body activity. Taken together, these results strongly suggest a role of LAMP in the pathogeny of SLE.     

Human monoclonal antibodies

Summary The technology for the production of murine monoclonal antibodies has been refined enormously since its introduction in 1975. However, the technology for generating human monoclonal antibodies has only recently come into its own. In this review, three currently available approaches to the production of human monoclonal antibodies are described. These include the hybridoma technique, based on the fusion of antibody-producing human B lymphocytes with either mouse or human myeloma or lymphoblastoid cells; the EBV immortalization technique, based on the use of Epstein-Barr virus (EBV) to immortalize antigen-specific human B lymphocytes; and the EBV-hybridoma technique, based on a combination of the first two methods.The EBV-hybridoma system retains the advantageous features of the other two systems while overcoming their pitfalls and may be the current method of choice for producing human monoclonal antibodies with a defined specificity.Recipient of a W.H.O. training scholarship in Tropical Diseases.Fellow of the National Cancer Institute of Canada.