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Therapeutic antibodies, for example Rituximab which recognises CD20 on B lymphoma cells, can cause adverse effects (e.g. http://www.ncbi.nlm.nih.gov/pubmed/19399690)

One reason behind these adverse effects could of course be an over-response of immune cells stimulated by the Fc region of antibodies attached to lymphona cells.

However, it could also be thinkable that the immune system launches a response against the antibody itself, recognising it as foreign. Does this occur? If so, what part of the injected antibody acts as the epitope recognised by immune cells as foreign?

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2 Answers 2

The short answer is that antibodies are proteins like any other, and if an antibody from a foreign source is injected it can result in an immune response. This is, of course, exploited in the production of secondary antibodies for use in research (e.g. goat anti-rabbit IgG is a goat antibody that recognises rabbit IgG).

Because of this, therapeutic antibodies are "humanised" and this is the case with Rituximab which is derived from a mouse monoclonal IgG:

Rituxan is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. The antibody is an IgG1 kappa immunoglobulin containing murine light- and heavy-chain variable region sequences and human constant region sequences. Rituximab is composed of two heavy chains of 451 amino acids and two light chains of 213 amino acids

Presumably it would be possible for the remaining mouse-derived variable regions to be recognised as foreign by the human immune system, and this possibility is hinted at in the abstract of an early paper on rituximab (McLaughlin et al. (1998) Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol.16:2825-33.) My emphasis...

A chimeric monoclonal antibody more effectively mediates host effector functions and is itself less immunogenic than are murine antibodies.

However, I'm not aware of any evidence that simple immune responses to Rituximab actually occur.

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You are correct that it is possible for the human immune system to detect remaining traces of "mouse-ness" in the variable regions of this particular monoclonal, as the humanization process was rather unsophisticated. Nowadays it is possible to take sequences from the mouse CDRs that are actually responsible for antigen binding and put them in a more human variable domain scaffold that is less likely to be antigenic to the host. –  MattDMo May 22 '13 at 21:31
    
In this case the real question would be, do foreign antibodies trigger an innate or a specific immune response, or both? If innate, what sort of pathogen pattern do they match? If specific, how are B and T lymphocytes specific to own Abs removed during negative selection (especially seeing as their specific sites could be specific to parts of an Ab antigen binding site)? –  Armatus May 22 '13 at 21:49
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It is unlikely that an antibody would bind another antibody within just the human species. Human antibodies which bind to the human Fc portion cannot exist as they would be filtered by self tolerance mechanisms (as these B cells would be chronically activated or would the T cells that would be required for costimulatory help allowing the B cells to class switch and make the antibodies). Antibodies that bind to other portions are possible but unlikely because they wouldn't be pathogenic thus wouldn't cause an inflammatory response so wouldn't be presented with the relevant danger signals to instruct T cells and B cells to respond. If they were CD8 T cells would rapidly destroy these B cells by binding to these B cells so again, no B cell antibodies recognising self antibodies.

There must be mechanisms to prevent this as if there weren't as B cell survival is dependent on its cognate antigen, if its cognate antigen were itself or other antibodies we would be in for deep trouble: namely a lymphoproliferative disorder is assume. But all this is off the top of my head, so guys correct me if I'm wrong.

I don't say there aren't B cells that can recognise antibodies, I just say they'll be deleted.

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