Skip Navigation LinksHome > December 2013 - Volume 13 - Issue 6 > B-cell memory and primary immune deficiencies: interleukin-...
Current Opinion in Allergy & Clinical Immunology:
doi: 10.1097/ACI.0000000000000009
PRIMARY IMMUNE DEFICIENCY DISEASE: Edited by Ramsay L. Fuleihan and Bruce D. Mazer

B-cell memory and primary immune deficiencies: interleukin-21 related defects

Desjardins, Marylina,b; Mazer, Bruce D.a,b

Collapse Box


Purpose of review: The purpose of this study is to describe recent advances in our understanding of the role of interleukin-21 (IL-21) in B-cell maturation, and how defects in IL-21 receptor (IL-21R) signalling pathways (IL-21R/γc/JAK3/STAT3) are related to primary immune deficiencies.

Recent findings: Abnormal signalling through IL-21R/γc/JAK3/STAT3 pathway has been related to decreased specific antibody responses following vaccination, and to increased susceptibility to encapsulated bacterial infections. This is manifested in the hyper-IgE syndrome, X-linked and JAK3-related severe combined immunodeficiency (SCID) and loss-of-function mutations in the IL-21R gene. Common variable immunodeficiency is associated with impaired in-vitro development of peripheral blood mononuclear cells or purified B-cells into memory or CD38+ B-cells following addition of IL-21.

Summary: IL-21 is a key cytokine in development of B-cells into immunoglobulin-secreting cells. Abnormal signalling through the IL-21R/γc/JAK3/STAT3 pathway leads to defective humoral immune responses to both T-dependent and T-independent antigens and impairs the establishment of long-lasting B-cell memory. Studies involving patients with hyper-IgE syndrome demonstrated the nonredundant role of STAT3 in B-cell production of high-affinity specific antibodies, while total serum immunoglobulins could be maintained through STAT3-independent activation of AID (activation-induced cytidine-deaminase). IL-21 related defects may also be associated with reduced natural killer (NK)-cell cytotoxicity and TH17 cytokine production, indicating that abnormalities in the IL-21-IL-21R pathway have profound effects on crucial immune responses.

© 2013 by Lippincott Williams & Wilkins, Inc.


Article Level Metrics

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.