Ig-Independent Igβ Expression on the Surface of B Lymphocytes after B Cell Receptor Aggregation

Kremyanskaya, Marina; Monroe, John G.

doi:10.4049/jimmunol.174.3.1501

Cited by 16 publications

(11 citation statements)

References 23 publications

(22 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most sIg-dissociated Ig␣/␤ heterodimers remain on the cell surface (39,40); however, our preliminary investigation indicated that Ig␣/␤ did not remain in association with CD20. BCR dissociation from CD20 may be necessary to allow CD20 to remain at the cell surface while antigen-bound receptors are internalized, or it may regulate the function of CD20.…”

Section: Discussionmentioning

confidence: 81%

CD20 Homo-oligomers Physically Associate with the B Cell Antigen Receptor

Polyak¹,

Li²,

Shariat

et al. 2008

Journal of Biological Chemistry

112

View full text Add to dashboard Cite

B cell antigen receptor (BCR) signaling initiates sustained cellular calcium influx necessary for the development, differentiation, and activation of B lymphocytes. CD20 is a B cell-restricted tetraspanning protein organized in the plasma membrane as multimeric molecular complexes involved in BCR-activated calcium entry. Using coprecipitation of native CD20 with tagged or truncated forms of the molecule, we provide here direct evidence of CD20 homo-oligomerization into tetramers. Additionally, the function of CD20 was explored by examining its association with surface-labeled and intracellular proteins before and after BCR signaling. Two major surface-labeled proteins that coprecipitated with CD20 were identified as the heavy and light chains of cell surface IgM, the antigen-binding components of the BCR. After activation, BCR-CD20 complexes dissociated, and phosphoproteins and calmodulin-binding proteins were transiently recruited to CD20. These data provide new evidence of the involvement of CD20 in signaling downstream of the BCR and, together with the previously described involvement of CD20 in calcium influx, the first evidence of physical coupling of the BCR to a calcium entry pathway.Signaling from the BCR, 4 which is composed of antigenbinding immunoglobulin (Ig) and signaling Ig␣/Ig␤ subunits, is necessary for the development, differentiation, and activation of B lymphocytes. Tyrosine kinase-dependent activation of phospholipase C-␥2, one of many intracellular signaling events that follow BCR ligation, leads to rapid release of calcium from the lumen of the endoplasmic reticulum into the cytoplasm. Depletion of the intracellular calcium stores triggers a second phase of calcium mobilization, characterized by sustained calcium entry into the cell via plasma membrane-associated "store-operated" calcium entry (SOCE) channels (1, 2). The amplitude and duration of the calcium response is translated into differential gene expression by calcium-sensitive proteins, determining the cellular response to receptor engagement (3-5).Key molecular components of SOCE have recently been identified with the discovery and characterization of the endoplasmic reticulum calcium sensor, STIM1, and the pore-forming subunit of the Icrac channel, Orai1 (2, 4, 6). A point mutation in Orai1 causes a form of hereditary severe combined immune deficiency syndrome, emphasizing the importance of intracellular calcium in lymphocyte physiology. However, although SOCE is absent in T lymphocytes from these patients, SOCE in B lymphocytes is reduced but not abolished, indicating additional SOCE pathways in the B cell lineage (1, 7).Increasing evidence has indicated that CD20, a B cell-restricted member of the MS4A (multispanning 4A) family of tetraspanins, functions in calcium entry. Intracellular calcium levels were increased in non-B cells ectopically expressing CD20 by transfection, and a calcium-mediated current, similar to that observed in B cells, was detected by whole cell patch clamp analysis (8, 9). BCR-activated calcium entry was ...

show abstract

Section: Discussionmentioning

confidence: 81%

CD20 Homo-oligomers Physically Associate with the B Cell Antigen Receptor

Polyak¹,

Li²,

Shariat

et al. 2008

Journal of Biological Chemistry

112

View full text Add to dashboard Cite

show abstract

“…It is thus feasible that the Igβ/CD19 module also plays a role on normal B cells. For example, it has been found that after their activation, splenic B cells rapidly internalize their BCR but still can be stained with anti‐Igβ antibodies although they are mIg negative (Kremyanskaya & Monroe, 2005). It was suggested that upon ligation, the BCR complex is destabilized so that the mIg molecule is separated from the Igα/Igβ heterodimer which stays alone on the B‐cell surface.…”

Section: Discussionmentioning

confidence: 99%

Continuous signaling of CD 79b and CD 19 is required for the fitness of Burkitt lymphoma B cells

Kläsener

Iype

et al. 2018

The EMBO Journal

View full text Add to dashboard Cite

Expression of the B‐cell antigen receptor (BCR) is essential not only for the development but also for the maintenance of mature B cells. Similarly, many B‐cell lymphomas, including Burkitt lymphoma (BL), require continuous BCR signaling for their tumor growth. This growth is driven by immunoreceptor tyrosine‐based activation motif (ITAM) and PI3 kinase (PI3K) signaling. Here, we employ CRISPR/Cas9 to delete BCR and B‐cell co‐receptor genes in the human BL cell line Ramos. We find that Ramos B cells require the expression of the BCR signaling component Igβ (CD79b), and the co‐receptor CD19, for their fitness and competitive growth in culture. Furthermore, we show that in the absence of any other BCR component, Igβ can be expressed on the B‐cell surface, where it is found in close proximity to CD19 and signals in an ITAM‐dependent manner. These data suggest that Igβ and CD19 are part of an alternative B‐cell signaling module that use continuous ITAM/PI3K signaling to promote the survival of B lymphoma and normal B cells.

show abstract

“…The ppc1-5/ 1 B cells exhibited increased levels of MHC class II, CD69, and B7.2, and decreased level of CD79b (Ig-␤ chain of the BCR) (Fig. 7A), indicating BCR engagement/activation (57)(58)(59)(60).…”

Section: The Phenotype Of Ppc1-5h/ 1 B Cellsmentioning

confidence: 99%

B Cells Expressing a Natural Polyreactive Autoantibody Have a Distinct Phenotype and Are Overrepresented in Immunoglobulin Heavy Chain Transgenic Mice

Tian¹,

Beardall²,

Xu³

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

Despite stringent regulation of disease-associated autoantibodies, a substantial proportion of circulating Abs in sera of healthy individuals exhibit self-reactivity. These Abs are referred to as naturally occurring or natural autoantibodies (NAAs). To understand the origin and function of NAAs, we have generated a new site-directed transgenic mouse model in which a prerearranged VDJ gene coding for the H chain of a typical polyreactive NAA, ppc1-5, is inserted into the IgH locus. This H chain, when combined with its original L chain, the λ1 L chain, yields a NAA that characteristically binds a variety of self and non-self Ags including ssDNA, actin, ubiquitin, and nitrophenyl phosphocholine. Despite their autoreactivity, B cells expressing ppc1-5H/λ1 NAA are not negatively selected, but rather are overrepresented in the transgenic mice. The shift toward λ1 expression mainly occurs during the transition of immature to mature B cells in the spleen, suggesting a BCR selection process. The ppc1-5H/λ1 B cells exhibit a phenotype that is different from those of the known mature B cell populations, and they are located predominantly in the lymphoid follicles of the spleen and the lymph nodes. These B cells are functionally active, producing high levels of Abs in vivo and responding well to BCR stimulation in vitro. The findings indicate that the ppc1-5/λ1 natural autoantibodies originate from a distinct B cell subset that may be positively selected by virtue of its poly/autoreactivity.

show abstract

Ig-Independent Igβ Expression on the Surface of B Lymphocytes after B Cell Receptor Aggregation

Cited by 16 publications

References 23 publications

CD20 Homo-oligomers Physically Associate with the B Cell Antigen Receptor

CD20 Homo-oligomers Physically Associate with the B Cell Antigen Receptor

Continuous signaling of CD 79b and CD 19 is required for the fitness of Burkitt lymphoma B cells

B Cells Expressing a Natural Polyreactive Autoantibody Have a Distinct Phenotype and Are Overrepresented in Immunoglobulin Heavy Chain Transgenic Mice

Contact Info

Product

Resources

About