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Gene Review:

FCRL4 - Fc receptor-like 4

Homo sapiens

Synonyms: CD307d, FCRH4, Fc receptor homolog 4, Fc receptor-like protein 4, FcR-like protein 4, ...

Falini, B. et al., Tiacci, E. et al., Hatzivassiliou, G. et al., Miller, I. et al., Polson, A.G. et al., et al.

Falini, Tiacci, Pucciarini, Bigerna, Kurth, Hatzivassiliou, Droetto, Galletti, Gambacorta, Orazi, Pasqualucci, Miller, Kuppers, Dalla-Favera, Cattoretti, Polson, Zheng, Elkins, Chang, Du, Dowd, Yen, Tan, Hongo, Koeppen, Ebens,

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Disease relevance of FCRL4

Expression pattern of the human FcRH/IRTA receptors in normal tissue and in B-chronic lymphocytic leukemia [1].
Similarly, in mucosa-associated lymphoid tissue (MALT) lymphomas IRTA1 was mainly expressed by tumor cells involved in lympho-epithelial lesions [2].

High impact information on FCRL4

Both genes are selectively expressed in mature B cells: IRTA1 in marginal zone B cells and IRTA2 in centrocytes, marginal zone B cells, and immunoblasts [3].
IRTA1 and IRTA2, novel immunoglobulin superfamily receptors expressed in B cells and involved in chromosome 1q21 abnormalities in B cell malignancy [3].
By cloning the breakpoints of a (1;14) (q21;q32) chromosomal translocation in a myeloma cell line, we have identified two novel genes, IRTA1 and IRTA2, encoding cell surface receptors homologous to the Fc and inhibitory receptor families [3].
The expression of the 28-kDa protein in normal lymphohematopoietic tissues was restricted to B cells and plasma cells and clearly differed from that expected for IRTA1 (selectively expressed by mucosa-associated lymphoid tissue [MALT] marginal zone B cells) [4].
We generated a murine monoclonal antibody (B28p) detecting an antigenic determinant shared by the immunoglobulin superfamily receptor translocation-associated 1 (IRTA1) receptor (the immunogen used to raise B28p) and an unrelated 28-kDa protein that was subsequently subjected to extensive characterization [4].

Biological context of FCRL4

We have now characterized and comparatively analyzed the structure and expression pattern of the entire family of IRTA genes, which includes 5 members contiguously located on chromosome 1q21 [5].
IRTA1 (immunoglobulin superfamily receptor translocation-associated 1) is a novel surface B-cell receptor related to Fc receptors, inhibitory receptor superfamily (IRS), and cell adhesion molecule (CAM) family members and we mapped for the first time its distribution in human lymphoid tissues, using newly generated specific antibodies [2].
As part of the almond breeding programme at IRTA, we investigated the S genotypes of several cultivars using a combination of RNase zymograms, testcrosses, pollen-tube growth analysis and molecular identification by PCR analysis [6].

Anatomical context of FCRL4

These structural features suggest that the IRTA receptors may play a role in regulating activation of normal B cells and possibly in the development of neoplasia [5].
A new family of Ig domain receptors referred to as the immune receptor translocation-associated (IRTA) proteins, FcR homologs (FcRHs) or FcR-like that are expressed in lymphoid cells has been recently described [1].
FcRH4/IRTA1 was expressed in a sub-population of memory B cells associated with mucosal tissue [1].
In contrast, no or a low number of IRTA1+ cells was usually observed in the marginal zone of mesenteric lymph nodes and spleen [2].
The immunohistochemical finding in the tonsil epithelial areas of aggregates of IRTA1+ B cells closely adjacent to plasma cells surrounding small vessels suggests antigen-triggered in situ proliferation/differentiation of memory IRTA1+ cells into plasma cells [2].

Other interactions of FCRL4

The IRTA1 and IRTA2 genes encode immunoglobulinlike cell surface receptors expressed in B cells and involved in chromosome 1q21 translocations in B-cell malignancy [5].
TMA were tested with specific antibodies against CD10, CD20, CD30, CD79a, CD138, Bcl-2, Bcl-6, IRF4, and IRTA1 [7].
T-bet-positive and IRTA1-positive monocytoid B cells differ from marginal zone B cells and epithelial-associated B cells in their antigen profile and topographical distribution [8].

Analytical, diagnostic and therapeutic context of FCRL4

Polymerase chain reaction (PCR) analysis of single tonsil IRTA1+ cells showed they represent a mixed B-cell population carrying mostly mutated, but also unmutated, IgV genes [2].

References

Expression pattern of the human FcRH/IRTA receptors in normal tissue and in B-chronic lymphocytic leukemia. Polson, A.G., Zheng, B., Elkins, K., Chang, W., Du, C., Dowd, P., Yen, L., Tan, C., Hongo, J.A., Koeppen, H., Ebens, A. Int. Immunol. (2006) [Pubmed]
Expression of the IRTA1 receptor identifies intraepithelial and subepithelial marginal zone B cells of the mucosa-associated lymphoid tissue (MALT). Falini, B., Tiacci, E., Pucciarini, A., Bigerna, B., Kurth, J., Hatzivassiliou, G., Droetto, S., Galletti, B.V., Gambacorta, M., Orazi, A., Pasqualucci, L., Miller, I., Kuppers, R., Dalla-Favera, R., Cattoretti, G. Blood (2003) [Pubmed]
IRTA1 and IRTA2, novel immunoglobulin superfamily receptors expressed in B cells and involved in chromosome 1q21 abnormalities in B cell malignancy. Hatzivassiliou, G., Miller, I., Takizawa, J., Palanisamy, N., Rao, P.H., Iida, S., Tagawa, S., Taniwaki, M., Russo, J., Neri, A., Cattoretti, G., Clynes, R., Mendelsohn, C., Chaganti, R.S., Dalla-Favera, R. Immunity (2001) [Pubmed]
Tumor protein D52 (TPD52): a novel B-cell/plasma-cell molecule with unique expression pattern and Ca(2+)-dependent association with annexin VI. Tiacci, E., Orvietani, P.L., Bigerna, B., Pucciarini, A., Corthals, G.L., Pettirossi, V., Martelli, M.P., Liso, A., Benedetti, R., Pacini, R., Bolli, N., Pileri, S., Pulford, K., Gambacorta, M., Carbone, A., Pasquarello, C., Scherl, A., Robertson, H., Sciurpi, M.T., Alunni-Bistocchi, G., Binaglia, L., Byrne, J.A., Falini, B. Blood (2005) [Pubmed]
IRTAs: a new family of immunoglobulinlike receptors differentially expressed in B cells. Miller, I., Hatzivassiliou, G., Cattoretti, G., Mendelsohn, C., Dalla-Favera, R. Blood (2002) [Pubmed]
Self-incompatibility genotypes in almond re-evaluated by PCR, stylar ribonucleases, sequencing analysis and controlled pollinations. López, M., Mnejja, M., Rovira, M., Collins, G., Vargas, F.J., Arús, P., Batlle, I. Theor. Appl. Genet. (2004) [Pubmed]
Identification of outcome predictors in diffuse large B-cell lymphoma. Immunohistochemical profiling of homogeneously treated de novo tumors with nodal presentation on tissue micro-arrays. Zinzani, P.L., Dirnhofer, S., Sabattini, E., Alinari, L., Piccaluga, P.P., Stefoni, V., Tani, M., Musuraca, G., Marchi, E., Falini, B., Baccarani, M., Pileri, S.A. Haematologica (2005) [Pubmed]
T-bet-positive and IRTA1-positive monocytoid B cells differ from marginal zone B cells and epithelial-associated B cells in their antigen profile and topographical distribution. Jöhrens, K., Shimizu, Y., Anagnostopoulos, I., Schiffmann, S., Tiacci, E., Falini, B., Stein, H. Haematologica (2005) [Pubmed]

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