The Molecular Basis of Lymphoid Architecture and B cell Res-ponses: Implications for Immunodeficiency and Immunopathology

Title: The Molecular Basis of Lymphoid Architecture and B cell Res-ponses: Implications for Immunodeficiency and Immunopathology

Volume: 1 Issue: 6

Author(s): Carola G. Vinuesa and Matthew C. Cook

Affiliation:

Keywords: Immunodeficiency and Immunopathology, Immune responses, B cell receptor, organogenesis, BCR ligation, B Cell Homeostasis, Blimp, (B cell specific activator protein), Streptococcus pneumoniae, Myasthenia Gravis, Ectopic lymphogenesis

Abstract: 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, Sjogrens syndrome and Hashimotos thyroiditis lymphoid organogenesis may be recapitulated in non-lymphoid parenchyma, under the influence of molecular interactions similar to those that operate during embryogenesis.

Cite this article as:

Vinuesa G. Carola and Cook C. Matthew, The Molecular Basis of Lymphoid Architecture and B cell Res-ponses: Implications for Immunodeficiency and Immunopathology, Current Molecular Medicine 2001; 1 (6) . https://dx.doi.org/10.2174/1566524013363276