Editors' ChoiceImmunology

Adrenergic Regulation of Antibodies

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Science Signaling  03 Dec 2013:
Vol. 6, Issue 304, pp. ec296
DOI: 10.1126/scisignal.2004957

B cells secrete immunoglobulin E (IgE) antibodies, which mediate allergic responses and play a role in the pathogenesis of allergic asthma. The amount of IgE secreted by B cells is regulated, in part, by CD23, a C-type lectin that acts as a low-affinity receptor for IgE. Binding of IgE to CD23 on the B cell surface inhibits IgE production; however, CD23 can be cleaved by ADAM10 (a disintegrin and metalloproteinase 10), and soluble CD23 (sCD23) binds to other receptors on B cells to stimulate IgE production. Noting that the β2-adrenergic receptor (β2AR) agonist norepinephrine is released from nerves in lymphoid tissue in response to antigen, and that the serum concentrations of IgE and sCD23 are decreased in immunized norepinephrine-depleted mice compared with those in control mice, Padro et al. investigated the mechanism by which β2-AR signaling stimulated IgE production. Mouse B cells stimulated (“primed”) with CD40L and interleukin-4 (IL-4) that were then treated with the β2-AR agonist terbutaline had increased amounts of ADAM10 and CD23 proteins compared with those of primed B cells not stimulated through the β2-AR; however, these proteins were present in exosomes (vesicles that are released from cells) rather than at the cell surface. The β2-AR–dependent increase in these proteins in exosomes occurred as early as 2 days after stimulation and depended on protein kinase A and p38 mitogen-activated protein kinase signaling. Recipient primed B cells that received exosomes from β2-AR–stimulated primed B cells produced more IgE per cell than did primed B cells that received exosomes from primed B cells not stimulated through the β2-AR or from β2-AR–deficient primed B cells that were stimulated with terbutaline. Together, these data suggest that β2-AR signaling in B cells enhances IgE production by stimulating the accumulation of ADAM10 and CD23 proteins in exosomes that then increase IgE secretion by recipient B cells.

C. J. Padro, T. M. Shawler, M. G. Gormley, V. M. Saunders, Adrenergic regulation of IgE involves modulation of CD23 and ADAM10 expression on exosomes. J. Immunol. 191, 5383–5397 (2013). [PubMed]

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