Antibody Deficiencies Defects in B Cell Development and Activation

Whereas defects in T cell development or in both T and B cell development contribute to the SCID phenotype,

TABLE 20-4 Antibody Deficiencies

Disease

Functional Deficiencies

Mechanism of Defect

Agammaglobulinemias

X-linked

Decrease in all serum Ig isotypes; reduced B cell numbers

Pre-B receptor checkpoint defect; Btk mutation

Autosomal recessive forms

Decrease in all serum Ig isotypes; reduced B cell numbers

Pre-B receptor checkpoint defect; mutations in IgM heavy chain (|), surrogate light chains (A.5), Iga, BLNK

Hypogammaglobulinemias/isotype defects

Selective IgA deficiency

Decreased IgA; may be associated with increased susceptibility to bacterial infections and protozoa such as Giardia lamblia

Mutations in TACI in some patients

Selective IgG2 deficiency

Increased susceptibility to bacterial infections

Small subset have deletion in IgH y2 locus

Common variable immunodeficiency

Hypogammaglobulinemia; normal or decreased B cell numbers

Mutations in ICOS and TACI in some patients

ICF syndrome

Hypogammaglobulinemia, occasional mild T cell defects

Mutations in DNMT3B

Hyper-IgM syndromes

X-linked

Defects in T helper cell-mediated B cell, macrophage, and dendritic cell activation; defects in somatic mutation, class switching, and germinal center formation; defective cell-mediated immunity

Mutation in CD40L

Autosomal recessive with cellmediated immune defects

Defects in T helper cell-mediated B cell, macrophage, and dendritic cell activation; defects in somatic mutation, class switching, and germinal center formation; defective cell-mediated immunity

Mutations in CD40, NEMO

Autosomal recessive with antibody defect only

Defects in somatic mutation and isotype switching

Mutations in AID, UNG

AID, activation-induced cytidine deaminase; DNMT3B, DNA methyltransferase 3B; ICF, immunodeficiencies-centromeric instability-facial anomalies; ICOS, inducible costimulator; NEMO, NF-kB essential modulator; TACI, transmembrane activator and calcium modulator and cyclophilin ligand interactor; UNG, uracil N-glycosylase.

more circumscribed defects in B cells result in disorders in which the primary abnormality is in antibody synthesis (Table 20-4). Some of these disorders are caused by defects in B cell development (see Fig. 20-1) and others by abnormal B cell activation and antibody production (Fig. 20-2). However, in one subset of hyper-IgM syndromes discussed later, antibody deficiencies are also accompanied by defects in macrophage and APC activation, which in turn result in attenuated cell-mediated immunity.

Was this article helpful?

0 0
How To Bolster Your Immune System

How To Bolster Your Immune System

All Natural Immune Boosters Proven To Fight Infection, Disease And More. Discover A Natural, Safe Effective Way To Boost Your Immune System Using Ingredients From Your Kitchen Cupboard. The only common sense, no holds barred guide to hit the market today no gimmicks, no pills, just old fashioned common sense remedies to cure colds, influenza, viral infections and more.

Get My Free Audio Book


Post a comment