Table 1.

Selected Manifestations of Abnormal B cell Development

	Humoral Immunity
	Serum Immunoglobulins				Antibody Responses	Common Infections	Other Immunologic and Clinical Features
	M	G	A	E
PREDOMINANTLY B CELL DEFICIENCY
Failure to create immunoglobulin
Recombinase activating gene (RAG 1/2) deficiency	↓	↓	↓	↓	−	bacteria, viruses, fungi	May present with Omenn Syndrome
Artemis deficiency (SCIDA)	↓	↓	↓	↓	−	"	Radiation sensitivity, may present with Omenn Syndrome
Cernunnos Deficiency	↓	↓	↓	↓	−	"	Radiation sensitivity
DNA Ligase IV (LIG4) deficiency	↓	↓	↓	↓	−	"	Radiation sensitivity, may present with Omenn syndrome
Failure to create the BCR
Autosomal agammaglobulinemia
Recessive: λ5, VpreB, Igα (CD79a), Igβ (CD79a)	↓	↓	↓	↓	−	bacteria, Giardia lamblia	Normal numbers of pro-B cells
Failure to permit the BCR to transduce its signal
Autosomal agammaglobulinemia
Recessive: BLNK deficiency	↓	↓	↓	↓	−	bacteria, Giardia lamblia	Normal numbers of pro-B cells
X-linked agammaglobulinemia (BTK deficiency)	↓	↓	↓	↓	−	"	Normal numbers of pro-B cells
PREDOMINANTLY ANTIBODY DEFICIENCY
Failure of follicular T cell:B cell interactions
Hyper IgM syndrome
X-linked CD40 ligand deficiency	N/↑	↓	N/↓	↓	+/−	bacteria, viruses, fungi	ITP, AIHA, neutropenia, liver and biliary disease
X-linked IKK-gamma (NEMO) deficiency	N/↑	↓	↓	↓	+/−	"	Anhidrotic epidermal dysplasia, anti-polysaccharide deficiencies
CD40 deficiency	N/↑	↓	N/↓	↓	+/−	"	Neutropenia, gastrointestinal and liver/biliary tract disease
Failure to modify immunoglobulin genes
Hyper IgM syndrome
Activation-induced cytidine deaminase (AID) deficiency	N/↑	↓	↓	↓	+/−	bacteria	Lymphadenopathy
Uracil-DNA Glycosylase (UNG) deficiency	N/↑	↓	↓	↓	+/−	"	Lymphadenopathy
Alteration of BCR or B cell survival signals
CD20 deficiency	N/↑	N/↓	N		+/−	bacteria	Antipolysaccharide deficiency, decreased memory cells
Selective IgA deficiency (MHC-associated, TACI)	N	N	↓	N	+/−	bacteria, Giardia lamblia	SLE (2–5%), CD (3%), RA (2%), ITP (0.5%), AR, allergic rhinitis
Common variable immune deficiency (ICOS, TACI, BAFFR, CD19)	N/↓	↓	↓	↓	−	"	AIHA, ITP, ATD, SLE
Unknown
Selective inability to respond to bacterial polysaccharides	N	N	N	N	+/−	bacteria
Selective IgA deficiency (MHC-associated)	N	N	↓	N	+/−	bacteria, Giardia lamblia	SLE (2–5%), CD (3%), RA (2%), ITP (0.5%), AR
IgG subclass deficiency	N	N/↓	N/↓	N	+/−	+/− bacteria
Common variable immune deficiency (MHC-associated)	N/↓	↓	↓	↓	−	bacteria, Giardia lamblia	AIHA, ITP, ATD, SLE

^*AIHA - Autoimmune Hemolytic Anemia, ITP - Idiopathic Thrombocytopenic Purpura, SLE - systemic lupus erythematosus, ATD - Autoimmune Thyroid Disease CD - Celiac Disease, IDDM - Insulin Dependent Diabetes MKellitus, AR - Allergic Rhinitis, RA - rheumatoid arthritis