Figure 1.

Mechanisms of primary antibody deficiency. Schematic representation of B-cell development indicating (in red) points at which immunodeficiency syndromes may impair antibody production. Primary antibody deficiency can be due to failure of B-cell development in the bone marrow (e.g. agammaglobulinaemia syndromes), failure of B-cell egress from marrow (e.g. WHIM (warts, hypogammaglobulinaemia, infections and myelokathexis) syndrome), T-cell disorders (e.g. inducible costimulator (ICOS) deficiency), failure of Ig class-switching (hyper-IgM syndromes) or impairment of late B-cell development, proliferation and survival. CVID may be characterised by compromise of any or all of these late stages (red box delineated by dashed line) whereas other antibody deficiency syndromes affect only specific pathways. XLA: X-linked agammaglobulinaemia; BLNK: B-cell linker; def: deficiency; MHC II: major histocompatibility complex class II; BCR: B-cell receptor; CVID: common variable immunodeficiency disorders; BAFF: B-cell activating factor; APRIL: a proliferation-inducing ligand; TACI: transmembrane activator CAML (calcium modulator and cyclophilin ligand) interactor; BAFF-R: BAFF receptor; AID: activation-induced cytidine deaminase; Spec ab: specific antibody.