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Curr Mol Med. 2001 Dec;1(6):689-725.

The molecular basis of lymphoid architecture and B cell responses: implications for immunodeficiency and immunopathology.

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Medical Genome Center, John Curtin School of Medical Research, Australian National University, Canberra, ACT.


Immune responses usually take place in secondary lymphoid organs such as spleen and lymph nodes. Most lymphocytes within these organs are in transit, yet lymphoid organ structure is highly organized; T and B cells segregate into separate regions. B cell compartments include naïve cells within follicles, marginal zones and B-1 cells. Interactions between TNF family molecules on hematopoietic cells and their receptors on mesenchymal cells guide the initial phase of lymphoid organogenesis, and regulate chemokine secretion that mediates subsequent T-B cell segregation. Recruitment of B cells into different compartments depends on both the milieu established during organogenesis, and the threshold for B cell receptor signaling, which is modulated by numerous coreceptors. Novel intrafollicular (germinal center) and extrafollicular (plasma cell) compartments are established when B cells respond to antigen. These divergent B cell responses are mediated by different patterns of gene expression, and influenced again by BCR signaling threshold and cellular interactions that depend on normal lymphoid architecture. Aberrant B cell responses are reviewed in the light of these principles taking into account the molecular and architectural aspects of immunopathology. Histological features of immunodeficiency reflect defects of B cell recruitment or differentiation. B cell hyper-reactivity may arise from altered BCR signaling thresholds (autoimmunity), defects in stimuli that guide differentiation in response to antigen (follicular hyperplasia vs plasmacytosis), or defective B cell gene expression. Interestingly, in diseases such as rheumatoid arthritis, Sjogren's syndrome and Hashimoto's thyroiditis lymphoid organogenesis may be recapitulated in non-lymphoid parenchyma, under the influence of molecular interactions similar to those that operate during embryogenesis.

[Indexed for MEDLINE]

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