The expression of murine B cell CD23, in vivo, is regulated by its ligand, IgE.
CD23, the low-affinity IgE receptor, is believed to participate in immune responses by mediating antigen capture for presentation by B cells and by shedding fragments with immunomodulatory properties. The number of CD23 molecules on B cells is increased during allergic responses and infection with helminths. This can be attributed in part to regulation of CD23 expression by cytokines, including IL-4. In addition, there is evidence that CD23 can be induced on cultured B cells by its ligand, IgE. In the current study we use IgE-deficient (IgE-/-) mice to establish the effects of IgE on CD23 expression by B cells in vivo, in the absence of allergic or parasitic stimuli. The spleens of IgE-/- and wild-type mice contained similar proportions of CD23+ B lymphocytes. However, cells from IgE-/- mice were found to have nearly 3-fold less CD23 on their surface. The mutant B cells had a corresponding defect in their ability to bind IgE. CD23 could be normally induced on IgE-/- B cells after culture with IL-4 or CD40 ligand, indicating that these cells had no inherent defect in CD23 biosynthesis. CD23 expression and IgE-binding capacity were both restored when splenocytes from IgE-/- mice were cultured in the presence of IgE. IgE-induced up-regulation of CD23 could be elicited in vivo as well. In IgE-/- mice, i.v. infusion of IgE corrected CD23 expression to wild-type levels. Our results demonstrate that IgE directly participates in CD23 regulation in vivo. This positive feedback loop may constitute a mechanism for the amplification of ongoing allergic responses.
Kisselgof
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Division of Immunology, Enders 8, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Oettgen
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D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D007073:Immunoglobulin E / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology*; D007143:Immunoglobulin Heavy Chains; D008024:Ligands; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D017455:Receptors, IgE / Q000096:biosynthesis*
D007143:Immunoglobulin Heavy Chains; D008024:Ligands; D012333:RNA, Messenger; D017455:Receptors, IgE; D007073:Immunoglobulin E