Mohamed ElTanbouly
@plasmacellguy.bsky.social
Well, a Treg is a T cell.
Although another Nobel laureate thinks (thought?) otherwise
pmc.ncbi.nlm.nih.gov/articles/PMC...
Although another Nobel laureate thinks (thought?) otherwise
pmc.ncbi.nlm.nih.gov/articles/PMC...
October 6, 2025 at 3:03 PM
Well, a Treg is a T cell.
Although another Nobel laureate thinks (thought?) otherwise
pmc.ncbi.nlm.nih.gov/articles/PMC...
Although another Nobel laureate thinks (thought?) otherwise
pmc.ncbi.nlm.nih.gov/articles/PMC...
I tried to access but it says that it's only available to Harvard folks
What am I missing? Aside from a Harvard ID card
What am I missing? Aside from a Harvard ID card
January 25, 2025 at 12:28 AM
I tried to access but it says that it's only available to Harvard folks
What am I missing? Aside from a Harvard ID card
What am I missing? Aside from a Harvard ID card
1-Incredible figure presentation and clarity
2-Eight years of work
3-Favorite statement (reminded me of another statement in an equally authoritative paper). Both are presented in screenshots below.
4-Builds upon earlier work by Peng et al from Jameson group
www.sciencedirect.com/science/arti...
2-Eight years of work
3-Favorite statement (reminded me of another statement in an equally authoritative paper). Both are presented in screenshots below.
4-Builds upon earlier work by Peng et al from Jameson group
www.sciencedirect.com/science/arti...
December 29, 2024 at 4:41 PM
1-Incredible figure presentation and clarity
2-Eight years of work
3-Favorite statement (reminded me of another statement in an equally authoritative paper). Both are presented in screenshots below.
4-Builds upon earlier work by Peng et al from Jameson group
www.sciencedirect.com/science/arti...
2-Eight years of work
3-Favorite statement (reminded me of another statement in an equally authoritative paper). Both are presented in screenshots below.
4-Builds upon earlier work by Peng et al from Jameson group
www.sciencedirect.com/science/arti...
Not useless...Technologies are ephemeral but ideas and insights are not :)
I was reading this Cell issue celebrating Molecular Biology and this comment is along the lines you described. Amazing how long it took to sequence a bit of DNA.
www.cell.com/cell/fulltex...
I was reading this Cell issue celebrating Molecular Biology and this comment is along the lines you described. Amazing how long it took to sequence a bit of DNA.
www.cell.com/cell/fulltex...
December 1, 2024 at 7:29 PM
Not useless...Technologies are ephemeral but ideas and insights are not :)
I was reading this Cell issue celebrating Molecular Biology and this comment is along the lines you described. Amazing how long it took to sequence a bit of DNA.
www.cell.com/cell/fulltex...
I was reading this Cell issue celebrating Molecular Biology and this comment is along the lines you described. Amazing how long it took to sequence a bit of DNA.
www.cell.com/cell/fulltex...
6) The hinge region of antibodies determines its agonistic potential or lack thereof
e.g. human IgG2 (h2b isoform) enhances agonistic activities of Abs (through disulfide shuffling) independent of higher-order crosslinking via FcγRs.
PMID: 25500122
www.sciencedirect.com/science/arti...
e.g. human IgG2 (h2b isoform) enhances agonistic activities of Abs (through disulfide shuffling) independent of higher-order crosslinking via FcγRs.
PMID: 25500122
www.sciencedirect.com/science/arti...
November 26, 2024 at 4:58 PM
6) The hinge region of antibodies determines its agonistic potential or lack thereof
e.g. human IgG2 (h2b isoform) enhances agonistic activities of Abs (through disulfide shuffling) independent of higher-order crosslinking via FcγRs.
PMID: 25500122
www.sciencedirect.com/science/arti...
e.g. human IgG2 (h2b isoform) enhances agonistic activities of Abs (through disulfide shuffling) independent of higher-order crosslinking via FcγRs.
PMID: 25500122
www.sciencedirect.com/science/arti...
5) Transcytosis: of antibodies through cells (including blood-brain barrier and lung epithelium...etc) via polymeric Ig receptor (pIgR) on these cells
This explain early observations of lung epithelial cells shining with intracellular IgA
PMID: 781899
bit.ly/Soutar1976
This explain early observations of lung epithelial cells shining with intracellular IgA
PMID: 781899
bit.ly/Soutar1976
November 26, 2024 at 4:57 PM
5) Transcytosis: of antibodies through cells (including blood-brain barrier and lung epithelium...etc) via polymeric Ig receptor (pIgR) on these cells
This explain early observations of lung epithelial cells shining with intracellular IgA
PMID: 781899
bit.ly/Soutar1976
This explain early observations of lung epithelial cells shining with intracellular IgA
PMID: 781899
bit.ly/Soutar1976
4) Second IgG antibodies form hexamers on cell surface after binding antigen through noncovalent interaction via their Fc regions
This triggers the complement cascade
PMID: 24626930
bit.ly/Diebolder2014
Side-note: IgM is 100-1000 times better at activating complement than IgG
This triggers the complement cascade
PMID: 24626930
bit.ly/Diebolder2014
Side-note: IgM is 100-1000 times better at activating complement than IgG
November 26, 2024 at 4:55 PM
4) Second IgG antibodies form hexamers on cell surface after binding antigen through noncovalent interaction via their Fc regions
This triggers the complement cascade
PMID: 24626930
bit.ly/Diebolder2014
Side-note: IgM is 100-1000 times better at activating complement than IgG
This triggers the complement cascade
PMID: 24626930
bit.ly/Diebolder2014
Side-note: IgM is 100-1000 times better at activating complement than IgG
2) Fab arm exchange is where antibodies swap half-molecules creating natural bispecifics
The third constant domain (CH3) (of the Fc) is essential for this
A later study showed aa positions 409 (in humans) as essential for his
R409 --> exchange
K409 --> stable
PMID: 21841137
bit.ly/Labrijn
The third constant domain (CH3) (of the Fc) is essential for this
A later study showed aa positions 409 (in humans) as essential for his
R409 --> exchange
K409 --> stable
PMID: 21841137
bit.ly/Labrijn
November 26, 2024 at 4:53 PM
2) Fab arm exchange is where antibodies swap half-molecules creating natural bispecifics
The third constant domain (CH3) (of the Fc) is essential for this
A later study showed aa positions 409 (in humans) as essential for his
R409 --> exchange
K409 --> stable
PMID: 21841137
bit.ly/Labrijn
The third constant domain (CH3) (of the Fc) is essential for this
A later study showed aa positions 409 (in humans) as essential for his
R409 --> exchange
K409 --> stable
PMID: 21841137
bit.ly/Labrijn
1) I don't know how you feel about antibodies, but here are a couple of (less-known) fascinating studies that might enhance your affinity towards these molecules
One of these is Fab arm exchange
This naturally occurs in vivo in IgG4 antibodies
PMID: 17872445
bit.ly/Kolfschoten2...
One of these is Fab arm exchange
This naturally occurs in vivo in IgG4 antibodies
PMID: 17872445
bit.ly/Kolfschoten2...
November 26, 2024 at 4:50 PM
1) I don't know how you feel about antibodies, but here are a couple of (less-known) fascinating studies that might enhance your affinity towards these molecules
One of these is Fab arm exchange
This naturally occurs in vivo in IgG4 antibodies
PMID: 17872445
bit.ly/Kolfschoten2...
One of these is Fab arm exchange
This naturally occurs in vivo in IgG4 antibodies
PMID: 17872445
bit.ly/Kolfschoten2...
I agree about positioning. Yes. It remains unanswered.
But I think positioning and "help" are also elusive (incompletely understood) from the B cell side.
www.cell.com/immunity/ful...
But I think positioning and "help" are also elusive (incompletely understood) from the B cell side.
www.cell.com/immunity/ful...
November 12, 2023 at 7:11 PM
I agree about positioning. Yes. It remains unanswered.
But I think positioning and "help" are also elusive (incompletely understood) from the B cell side.
www.cell.com/immunity/ful...
But I think positioning and "help" are also elusive (incompletely understood) from the B cell side.
www.cell.com/immunity/ful...
Addendum 2: The 2nd showed that allergen-specific IgA antibodies are not protective per se (that "IgA is good and IgE is bad" oversimplification can be laid to rest)
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
November 12, 2023 at 8:42 AM
Addendum 2: The 2nd showed that allergen-specific IgA antibodies are not protective per se (that "IgA is good and IgE is bad" oversimplification can be laid to rest)
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Addendum 1: the Eisenbarth lab dispelled certain unsubstantiated notions about immunity, first showing that LPS (a TLR ligand known to induce Type I responses) can induce Th2 responses bit.ly/Eisenbarth02
November 12, 2023 at 8:40 AM
Addendum 1: the Eisenbarth lab dispelled certain unsubstantiated notions about immunity, first showing that LPS (a TLR ligand known to induce Type I responses) can induce Th2 responses bit.ly/Eisenbarth02
21/ pre-Plasma cells have certain interesting features A- They upregulate the canonical PC markers CD138 and also CD28 B-They upregulate Bcl-XL (Bcl2l1) which is an anti-apoptotic regulator shown to suppress ER-stress dependent apoptosis in PCs
bit.ly/Gaudette2014
bit.ly/Gaudette2014
November 11, 2023 at 1:37 PM
21/ pre-Plasma cells have certain interesting features A- They upregulate the canonical PC markers CD138 and also CD28 B-They upregulate Bcl-XL (Bcl2l1) which is an anti-apoptotic regulator shown to suppress ER-stress dependent apoptosis in PCs
bit.ly/Gaudette2014
bit.ly/Gaudette2014
20/We then wanted to examine differences between GC B cells destined to become PCs (aka Pre-plasma cells) versus those that go back to the GC for another cycle round so we performed Smartseq on these cells
November 11, 2023 at 1:36 PM
20/We then wanted to examine differences between GC B cells destined to become PCs (aka Pre-plasma cells) versus those that go back to the GC for another cycle round so we performed Smartseq on these cells
19/ But what was interesting is if you try to compare the mean affinity (Kd) between "Binders" from both GC and PCs, you will find no significant difference, indicating that what this shows is an enrichment in binder % among PCs (and not qualitatively higher affinity per cell)
November 11, 2023 at 1:35 PM
19/ But what was interesting is if you try to compare the mean affinity (Kd) between "Binders" from both GC and PCs, you will find no significant difference, indicating that what this shows is an enrichment in binder % among PCs (and not qualitatively higher affinity per cell)
18/And as expected these PC have a higher percentage of binders than contemporaneous GC B cells using both ELISA and more sensitive monomeric binding assays (BLI) and most of these binders are of the IGHV1-72 heavy chain as expected (orange)
November 11, 2023 at 1:35 PM
18/And as expected these PC have a higher percentage of binders than contemporaneous GC B cells using both ELISA and more sensitive monomeric binding assays (BLI) and most of these binders are of the IGHV1-72 heavy chain as expected (orange)
17/Glossing over many Bruegelian details, we found that over time genetically-labeled PCs were retaining the NP-binding heavy chain whereas GC B cells were diversifying
November 11, 2023 at 1:34 PM
17/Glossing over many Bruegelian details, we found that over time genetically-labeled PCs were retaining the NP-binding heavy chain whereas GC B cells were diversifying
14/As in previous work by Victora, Nussenzweig and Phan groups we used s.c. immunization of popliteal lymph nodes because these are particularly devoid of GC B cells and PCs in the absence of immunization, so at least early on, everything will be specific to your immunogen
November 11, 2023 at 1:33 PM
14/As in previous work by Victora, Nussenzweig and Phan groups we used s.c. immunization of popliteal lymph nodes because these are particularly devoid of GC B cells and PCs in the absence of immunization, so at least early on, everything will be specific to your immunogen
11/Building upon this and a lot of work, we addressed the same question in a polyclonal system using genetic lineage tracing in S1pr2.CreERT2 inducible fluorescent reporter which predominantly labels GC B cells (and some activated B cells) S1pr2 model
bit.ly/Shinnakasu2016
bit.ly/Shinnakasu2016
November 11, 2023 at 1:32 PM
11/Building upon this and a lot of work, we addressed the same question in a polyclonal system using genetic lineage tracing in S1pr2.CreERT2 inducible fluorescent reporter which predominantly labels GC B cells (and some activated B cells) S1pr2 model
bit.ly/Shinnakasu2016
bit.ly/Shinnakasu2016
10/ Using the same model they comprehensively show later that these high-affinity GCs complete their transition into PCs using help from T follicular helper cells (supporting earlier work showing that T cell help is critical for PC differentiation in GCs) bit.ly/Kr%C3%A4utle...
November 11, 2023 at 1:31 PM
10/ Using the same model they comprehensively show later that these high-affinity GCs complete their transition into PCs using help from T follicular helper cells (supporting earlier work showing that T cell help is critical for PC differentiation in GCs) bit.ly/Kr%C3%A4utle...
9/Using this elegant model, they track what mutation increases the affinity of these cells and show that predominantly, if not exclusively, the high-affinity GC B cells become PCs.
November 11, 2023 at 1:31 PM
9/Using this elegant model, they track what mutation increases the affinity of these cells and show that predominantly, if not exclusively, the high-affinity GC B cells become PCs.
7/Does affinity regulate B cell and plasma cell responses? If so, how? Many papers addressed this longstanding question bit.ly/Phan2006 bit.ly/49wRVLi bit.ly/OConnor2006 but I will discuss my favorite by
Phan et al.
Phan et al.
November 11, 2023 at 1:30 PM
7/Does affinity regulate B cell and plasma cell responses? If so, how? Many papers addressed this longstanding question bit.ly/Phan2006 bit.ly/49wRVLi bit.ly/OConnor2006 but I will discuss my favorite by
Phan et al.
Phan et al.
7/ Where does affinity enhancement take place? In a T-cell dependent response, answer is Germinal Centers (GCs) where B cells move between light and dark zones until they get sufficient T cell "help" into the PC compartment. bit.ly/3MC7yHu bit.ly/Victora22
November 11, 2023 at 1:29 PM
7/ Where does affinity enhancement take place? In a T-cell dependent response, answer is Germinal Centers (GCs) where B cells move between light and dark zones until they get sufficient T cell "help" into the PC compartment. bit.ly/3MC7yHu bit.ly/Victora22
6/On the molecular side, Eisen & Siskind showed antibody affinity against the immunogen increases proportionally throughout the response. bit.ly/EisenSiskind64
November 11, 2023 at 1:29 PM
6/On the molecular side, Eisen & Siskind showed antibody affinity against the immunogen increases proportionally throughout the response. bit.ly/EisenSiskind64
5/Other papers include bit.ly/Sprent1971 bit.ly/GowansMcGreg... Cooper et al. also showed the these lymphocytes are B cells bit.ly/Cooper1965 And Glick et al.'s popular Poultry paper ~a decade earlier bit.ly/Glick1956
November 11, 2023 at 1:28 PM
5/Other papers include bit.ly/Sprent1971 bit.ly/GowansMcGreg... Cooper et al. also showed the these lymphocytes are B cells bit.ly/Cooper1965 And Glick et al.'s popular Poultry paper ~a decade earlier bit.ly/Glick1956