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Tuesday, April 2, 2013

The B cell encyclopedia of lung disease



Lung disease researchers could be accused of an excessive focus on aberrant T cell mechanisms in studies of most airway diseases.  In this month’s issue, Kato and co-authors have elegantly restored some balance to this T cell biology-centric perspective [p933-957#].  In what can only be described as an encyclopedic version of a B cell immunology textbook, complete with impressive tables and illustrated figures, Kato et al. deliver the sum of current thinking and knowledge on B cell and plasma cell biology in the respiratory system. [Journal of Allergy and Clinical Immunology 2013;131(4):933-957]

The authors begin with a comprehensive review of adaptive immunity including B lymphocyte development, lineage differentiation and commitment in secondary lymphoid organs [SLO] under the influence of cytokines, class switch recombination, and chemokine-induced trafficking and recirculation.  Kato et al. discusses B cell and plasma cell localization and activation in the airway parenchyma, draining lymph nodes and mucosa.

In particular, Kato et al. cover B cell-associated diseases that manifest in the respiratory system, such as systemic lupus erythematosus [SLE], and the targeted therapies that are currently approved for treatment or undergoing clinical trials.  A few highlights:

•    Anti-IL-9, a Th cytokine that acts on B-cells and mast cells, is in clinical trials as a therapy for asthma.
•    Anti-IL-6 receptor, approved for use in the treatment of rheumatoid arthritis, has been proposed as therapy for asthma and COPD, and is in clinical trials for cancer treatment.
•    Anti-IFNα is in clinical trials for SLE.
•    Anti-BAFF has been approved for the treatment of SLE.

The authors review B lymphocyte organization in the airway, critical airway immunoglobulins and associated lung diseases, such as the hyper-Ig syndromes, and the commonality of excessive B cell expansion with subsequent loss of self-tolerance that characterizes certain lung diseases such as hypersensitivity pneumonitis, rheumatoid arthritis, and Sjogren’s disease.  They conclude posing important questions that remain, which are stalling the development of therapies. 



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