B cell/antibody tolerance to our own antigens.
The lymphoid system normally mounts damaging responses to infectious pathogens while avoiding equally damaging responses to self. A notable number of antibodies to self antigens are formed but normally remain at levels below the damaging threshold, only temporarily rising to damaging levels during protective responses against infectious nonself. Many mechanisms regulate the level of autoantibodies and anti-self B cells including deletion, anergy, ignorance for antigen, receptor editing, coinhibition, competition for resources to sustain B cell responses, and apoptotic denouement of damaging responses following the ejection or containment of foreign invaders. While infectious events may encourage immune responses to self antigens, infectious events tend also to strengthen regulatory mechanisms. When regulatory mechanisms do not function properly, abnormal damaging responses to self antigens may occur. While defects in a single regulatory mechanism may result in autoimmunity, this eventuality usually happens only on permissive genetic backgrounds; this indicates that weakness in other regulatory mechanisms may be necessary to result in the emergence of damaging responses to self antigens. The immune system and its regulatory mechanisms are not simple, as one would expect of a homoeostatic process that also has the ability to expand enormously when challenged and to contract rapidly when threats pass. These processes that avoid damaging anti-self B cells are much more complicated than that envisaged in standard two signal models. Simple signals through the B cell antigen-receptor probably encourage B cell survival and receptivity, while other signals (costimulatory or coinhibitory) promote B cell stimulation or non-stimulation/inactivation.
Sinclair
Nicholas R StC
NR
Department of Microbiology and Immunology, The University of Western Ontario, London, Ontario, N6A 5C1, Canada. nsinclai@rogers.com
D000818:Animals; D000906:Antibodies / Q000737:chemistry*; D000938:Antigen-Presenting Cells; D000941:Antigens / Q000737:chemistry; D017209:Apoptosis; D001324:Autoantigens / Q000737:chemistry*; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007107:Immune System; D007108:Immune Tolerance; D011947:Receptors, Antigen, B-Cell; D017634:Self Tolerance
D000906:Antibodies; D000941:Antigens; D001324:Autoantigens; D011947:Receptors, Antigen, B-Cell