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Med Hypotheses. 2007;68(1):158-61. Epub 2006 Aug 4.

Immunoglobulin is a highly diverse self-molecule that improves cellular diversity and function during immune reconstitution.

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Internal Medicine Department-Hematology Division, Mayo Clinic, Stabile building, 6th floor, 200th Street SW, Rochester, MN, USA.


Paradoxically, human B cell immune deficiencies are associated with increased susceptibility to viral and fungi infections, which are T cell immunity related infections. Also, some viral infections occurring in immune depressed patients such as cytomegalovirus infections are recommended to be treated with intravenous immunoglobulin (IVIg) in combination with antiviral therapy. This fact has no clear biological explanation but it has been shown to be successful. Recently, B cells and immunoglobulin were identified as essential elements driving T cell receptor (TCR) diversity generation. Idiotype peptides of B cell immunoglobulin may be the driving force for the antigen presenting function of B cells and other antigen presenting cells to influence the T cell repertoire. This seems to be another relevance of Jerne's idiotypic network and another function of immunoglobulin. Since T cells function depends on the diversity of the TCR repertoire, means to increase the diversity of the T cell repertoire may improve T cell function in situations characterized by a contracted TCR repertoire, such as AIDS, primary immunodeficiency, cancer, autoimmunity and following chemotherapy and hematopoietic precursors transplantation. The clinical hypothesis here put forward is that B cells and/or immunoglobulin may be used therapeutically aiming to increase and potentially to restore T cell repertoire diversity improving T cell function in situations implicating a contracted T cell repertoire. The fact that immunoglobulin influence the composition of T cell repertoire by increasing its diversity allows a much wider application of this molecule in the clinical practice. Here is presented a novel reasoning for the use of IVIg in humans, which should be explored. All the situations where immune reconstitution occurs are potentially a target for this therapeutically mechanism, aiming to fast and improve the diversity of the reconstituted immune repertoires. This new role of Ig molecule, an old and widely therapeutically used molecule, may help to explain several effects that IVIg have in the T cell compartment, such as modulation of the activation and function of effectors T cells. The idea that immunoglobulin is essential in the generation and maintenance of a diverse compartment of T cells, affecting T cell function via that mechanism suggests a promising approach to medical conditions involving immune reconstitution. Furthermore, it represents a new paradigm of understanding the immune system as a complex, interdependent web of cells/cell products that inter-affect each other generation, function and survival.

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