Perpetuation of immunological memory: a relay hypothesis.
A mechanism is proposed which explains the perpetuation of B-cell immunological memory indefinitely without requiring the presence of long-living memory cells or persisting antigen. The salient feature of this model is that immunological memory can be perpetuated indefinitely through the mutual interaction of idiotypic and anti-idiotypic B cells. These cells mutually stimulate and clonally expand with either specific or bystander T-cell help. Because B cells can present antigen, they present 'apparently foreign' idiopeptides to T cells. The idiopeptides of de novo synthesized antibody is presented to CD8+ T cells that recognize the idiopeptide-presenting cell as targets and regulate their population. The recycling of immunoglobulins from surface to endosomal compartment of B cells leads to the presentation of idiopeptides by major histocompatibility complex (MHC) class II to CD4+ T cells. Even if the majority of the clonally expanded cells die because of lack of stimulation, cytotoxic T lymphocyte (CTL) lysis or for other reasons, the surviving cells will be able to carry forward the memory. This mechanism also provides a means for affinity maturation through idiotypic selection of somatically mutated high affinity cells or those from the naïve pool. We have termed these two types of complementary B cells as Burnet B cells: those which recognize the antigen or antigen mimic, and Jerne B cells, which can recognize the idiotypes of antibody and carry antigen mimics. The proposed hypothesis can explain differential duration of memory for different antigens, the shelf space paradox, affinity maturation, repertoire shift, etc.
Nayak
R
R
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India. nayak@mcbl.iisc.ernet.in
Mitra-Kaushik
S
S
Shaila
M S
MS
D000818:Animals; D000915:Antibody Affinity; D001402:B-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D008211:Lymphocyte Cooperation / Q000276:immunology; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000276:immunology