B cell antigen receptors of the IgM and IgD classes are clustered in different protein islands that are altered during B cell activation

Maity, Palash Chandra; Blount, Amy L.; Jumaa, Hassan; Ronneberger, Olaf; Lillemeier, Björn F.; Reth, Michael

doi:10.1126/scisignal.2005887

Cited by 115 publications

(138 citation statements)

References 71 publications

(106 reference statements)

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“…Cortical actin can also promote interactions between membrane proteins through the regulation of their clustering. Recent superresolution imaging studies (Box 1) suggests that the BCR is present in the plasma membrane of resting B cells as a mixture of monomers and clusters of variable sizes 49,92,93 . The IgM BCR clusters are small, resembling previously described protein islands 94 .…”

Section: [H1] Cytoskeletal Regulation Of Bcr Signallingmentioning

confidence: 99%

Cytoskeletal control of B cell responses to antigens

Tolar

2017

Nat Rev Immunol

122

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The actin cytoskeleton is essential for cell mechanics and has increasingly been implicated in the regulation of cell signalling. In B cells, the actin cytoskeleton couples extensively to B cell receptor (BCR) signalling pathways and its defects can either enhance or suppress B cell activation. Recent insights from single-cell imaging and biophysical techniques suggest that actin orchestrates BCR signalling at the plasma membrane through effects on protein diffusion, and that it regulates antigen discrimination through the biomechanics of immune synapses. These mechanical functions also play a role in the adaptation of B cell subsets to specialized tasks during antibody responses.3

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Section: [H1] Cytoskeletal Regulation Of Bcr Signallingmentioning

confidence: 99%

Cytoskeletal control of B cell responses to antigens

Tolar

2017

Nat Rev Immunol

122

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“…IgD is more densely clustered on the cell surface than IgM into separate “islands” and is distinctly associated with co-receptors such as CD19, suggesting that these isotypes might exhibit qualitative differences in downstream signal transduction as well [29,30]. Since CD19 couples the BCR to the PI3K survival pathway, IgD and IgM may differentially support B cell survival independent of antigen sensing and surface expression.…”

Section: Tonic Bcr Signaling Is Essential For B Cell Survivalmentioning

confidence: 99%

Tonic Signals: Why Do Lymphocytes Bother?

Myers

Zikherman

Roose

2017

Trends in Immunology

100

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Since the 1990s it has been known that B- and T- lymphocytes exhibit low-level, constitutive signaling in the basal state (“tonic signaling”). These lymphocytes display a range of affinity for self, which generates a scale of tonic signaling. Surprisingly, what signaling pathways are active in the basal state and the functional relevance of the observed tonic signaling heterogeneity remain open questions today. Here we summarize what is known about the mechanistic and functional details of tonic signaling. We highlight recent advances that have increased our understanding of how the amount of tonic signal impacts immune function, describing novel tools that have moved the field forward and towards molecular understanding of tonic signaling.

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“…Mature B cells co‐express two different classes of BCR, namely the IgM‐BCR and the IgD‐BCR, which reside in different protein islands on the plasma membrane (Yang & Reth, 2010; Maity et al , 2015). On resting B cells, CD19 complex and the CD81‐tetraspanin complex are localized inside IgD‐class‐specific protein islands (Mattila et al , 2013; Maity et al , 2015).…”

Section: Introductionmentioning

confidence: 99%

“…On resting B cells, CD19 complex and the CD81‐tetraspanin complex are localized inside IgD‐class‐specific protein islands (Mattila et al , 2013; Maity et al , 2015). On activated B cells, however, the CD19 complex is found in close proximity to the open IgM‐BCR and thus gains access to ITAM signaling (Klasener et al , 2014).…”

Section: Introductionmentioning

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

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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.

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B cell antigen receptors of the IgM and IgD classes are clustered in different protein islands that are altered during B cell activation

Cited by 115 publications

References 71 publications

Cytoskeletal control of B cell responses to antigens

Cytoskeletal control of B cell responses to antigens

Tonic Signals: Why Do Lymphocytes Bother?

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

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