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BAFF-R deficiency

Definition

Primary antibody deficiency associated with a genetic defect in the gene encoding the “BAFF-receptor” (BAFF-R)

Clinical background

BAFF-R deficiency presents as mild hypogammaglobulinemia with preserved IgA production (1). World wide only 2 related persons have been identified (1). Only one of them presented with increased rates of respiratory infections, while the clinical course of the other has been unremarkable up to old age. Neither person suffers from autoimmune phenomena or lymphoproliferative disorder.

Immunologic background

BAFF-Receptor (BAFF-R) belongs to the TNF-R family and is exclusively expressed on B cells. It is closely related to TACI and BCMA. It is first expressed on B cells after reaching the immature / transitional stage (2). Therefore it has no function during the antigen independent development of B cells in the bone marrow. Both BAFF-R deficient patients presented with reduced B cell counts and a relative expansion of transitional B cells above 30% (1). The Marginal zone like B cells were more reduced than the class-switched memory B cells. IgA production was preserved, most likely due to an intact mucosal IgA plasma cell differentiation (1). While T dependent antibody responses seem to be intact, anti polysaccharide response was severely reduced in one tested patient (1).  The immunologic phenotype closely resembled the murine findings (3).

Animal models

Natural mutants (3) and knock out mice (4) demonstrate the important role of BAFF-R in the survival and differentiation of transitional B cells (5, 6). BAFF-R has only one known ligand BAFF (Blys) (7). The marginal zone B cells are especially dependent on BAFF-R signals while B1 B cell differentiation seems to be normal in the absence of BAFF-R (4). BAFF-R might play an additional role during early germinal center dependent memory differentiation (8). In the absence of BAFF-R both T dependent and independent responses are reduced in mice (4). While IgG and IgM serum levels are reduced in BAFF-R -/- mice, IgA serum levels are normal (4).

References

      1.   Warnatz K et al. (2009) B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans Proc Natl Acad Sci U S A 106(33): 13945-13950.

      2.   Rodig SJ, Shahsafaei A, Li B, Mackay CR, Dorfman DM (2005) BAFF-R, the major B cell-activating factor receptor, is expressed on most mature B cells and B-cell lymphoproliferative disorders Hum Pathol 36: 1113-1119.

      3.   Thompson JS et al. (2001) BAFF-R, a newly identified TNF receptor that specifically interacts with BAFF Science 293: 2108-2111.

      4.   Sasaki Y, Casola S, Kutok JL, Rajewsky K, Schmidt-Supprian M (2004) TNF family member B cell-activating factor (BAFF) receptor-dependent and -independent roles for BAFF in B cell physiology J Immunol 173: 2245-2252.

      5.   Batten M et al. (2000) BAFF mediates survival of peripheral immature B lymphocytes J Exp Med 192: 1453-1466.

      6.   Mackay F, Browning JL (2002) BAFF: a fundamental survival factor for B cells Nat Rev Immunol 2: 465-475.

      7.   Mackay F, Ambrose C (2003) The TNF family members BAFF and APRIL: the growing complexity Cytokine Growth Factor Rev 14: 311-324.

      8.   Zhang X et al. (2005) BAFF supports human B cell differentiation in the lymphoid follicles through distinct receptors Int Immunol 17: 779-788.

 

Last update: 2010-05-11 10:53:52
Immunologic phenotypes (BAFF-R deficiency)

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