Contemplating Langerhans and marginal zone B cells: they appear to deliver the antigens to FDC

Do lymphatic Langerhans deliver antigens to the Germinal center Follicular Dendritic Cell like the marginal zone B cells in the spleen?

Marginal zone B cells shuttle antigens to FDC
https://www.ncbi.nlm.nih.gov/pubmed/18037889

Langerhans promotes the GC-B/Tfh formation during a leishmania infection
https://www.ncbi.nlm.nih.gov/pubmed/25070244

cd169 mediates the capture of exosomes in lymph and spleen
https://www.ncbi.nlm.nih.gov/pubmed/24255917

cd169 cells : Marginal zone B,  langerhans, scs, and MM
scs
https://www.ncbi.nlm.nih.gov/pubmed/22675532?dopt=Abstract
https://www.ncbi.nlm.nih.gov/pubmed/22192781?dopt=Abstract

If only langerhans and Marginal zone B cells interact with the FDC giving it antigens then what do they have in common? (langerhans at the lymph and MZB at the spleen)

marginal zone B cell cancer followed by langerhans cancer in 77 year old
https://www.ncbi.nlm.nih.gov/pubmed/26286813

langerhans histocytosis following lymphoma
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839484/

langerhans histocytosis resembling marginal zone lymphoma
https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0714.2006.00436.x

epstein barr virus and marginal zone lymphoma
https://www.ncbi.nlm.nih.gov/pubmed/29228090
https://www.ncbi.nlm.nih.gov/pubmed/25692616
https://www.ncbi.nlm.nih.gov/pubmed/21552113

epstein barr is thought to bind cd21 but I believe it uses the estrogen alpha receptor

FDC and estrogen alpha receptor
https://ajp.amjpathol.org/article/S0002-9440(10)63490-6/pdf

estrogen promotes langerhans differentiation
https://www.ncbi.nlm.nih.gov/pubmed/16210618
https://www.researchgate.net/publication/7554414_Estrogen_Selectively_Promotes_the_Differentiation_of_Dendritic_Cells_with_Characteristics_of_Langerhans_Cells

estrogen favors marginal zone B cells
https://www.ncbi.nlm.nih.gov/pubmed/21107497

estrogen secreted by lymph tissue
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133356/
https://www.ncbi.nlm.nih.gov/pubmed/29486537

Benzene as the carcinogen: man who handled benzene developed marginal zone lymphoma
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605838/

alaska and benzene risk (thinking of my grandmother)
http://www.farnorthscience.com/2007/12/10/ak-sci-forum/benzene-exposure-in-anchorage/


Hypothesis Review:
alpha herpes use beta estrogen receptor hsv1 hsv2 zoster
beta herpes use estrogen related receptors cmz hhv6 hhv7
gamma herpes use alpha estrogen receptors EBV hhv8

marker for FDC is cd21
https://www.ncbi.nlm.nih.gov/pubmed/16280657

contemplating follicular T cells and B7-2

The B7 ligands inform the T cell which pathway to take: to become follicular T cells or to become regulator Tcells  then as a T follicular to find a B cell to make antibodies. B7 when binding CTL-4 can also slowly stop the reactions.

Capture of Antigen by BCR of B cell from FDC
https://www.ncbi.nlm.nih.gov/pubmed/19506051

cd169 macrophages APC (these are the SCS of the lymph and the metallophillic macrophage of the spleen)
https://onlinelibrary.wiley.com/doi/full/10.1002/eji.201444983

THfollicular Th1 to Tfh1 or Th2 to Tfh2 ?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193096/

Does B7-2 on APC cause the conversion of Th1 or Th2 to the follicular type of T cell? Tfh1 and Tfh2?

B7-2 and follicular T cell development
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3089765/

B7-2 is on Langerhans, medial zone B cells, macrophages, and dendritic cells which bring the antigens to the lymph or spleen

B7-1 is on the follicular B cell that presents to the follicular T cell that with TCR stimulation activates the T cell and Icos is expressed.

(B7-1 is also on activated T cells and activated macrophages)

Pd-L is increased with ifn gamma on cd4 and cd8 cells so they can interact with the myeloid or plasmacytoid dendritic cells.

B7-DC(pd-L1) on myeloid dendritic

B7-H1 (pd-L2) plasmacytoid dendritic

B7-1 (cd80) follicular B cells which present

B7-2 (cd86)  Langerhans, macrophages, dendritic cells, and marginal zone B cells (antigen carriers)

where the Th1 is actually a follicular Th1 and the Tc is a follicular Tc.  Note that I am not showing the interaction of the inner antigens on the scs macrophages antigen presenting to the B cells BCR.

CD8 T cells becoming follicular like
https://www.ncbi.nlm.nih.gov/pubmed/29743314

The notion that B7-2 tells the T cells to become follicular is logistical. The antigen carrier wearing B7-2 informs the T cell that we have the antigen so please find an antigen presenter, a B cell and make antibodies with them.

in the absence of additional dendritic/antigen carrying cells  the T cells having seen APC can't make il-21 ( become follicular?)
https://www.ncbi.nlm.nih.gov/pubmed/21715693/

Is this the B7-2 ?

Tfollicular cells and autoimmune disease
https://www.bioportfolio.com/resources/trial/161554/Study-the-Role-of-T-Lymphocytes-in-Autoimmune-Hemolytic-Anemia.html

How do B cells see the antigen for internal antigens? SCS macrophages are key

When you separate the inner and outer antigen pathways you can see where B cells become antigen presenters themselves but how do they see the antigens and make the proper antibody when the TCR of T cells are critical ?

In these scenarios we have left out the macrophages.  The SCS macrophages display viruses and antigens but macrophages are the "second stimulators".  They keep T cells activated and I believe they might also show the viral antigen to B cells that have been activated.

The macrophages are required for GC formation:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3647009/

The SCS macrophages present the viral antigens to the BCR of B cells
https://www.cell.com/fulltext/S0092-8674(07)01401-8
https://www.ncbi.nlm.nih.gov/pubmed/17934446?dopt=Abstract (flypaper)
http://iannaconelab.com/wp-content/uploads/2011/03/Ann-NY-Acad-Sci-2014-Kuka.pdf

scs, viral infections, and Nk
http://www.bloodjournal.org/content/bloodjournal/120/24/4744.full.pdf?sso-checked=true

the 3 lymph node macrophages divided into 3 groups
https://www.karger.com/Article/FullText/337007?id=pmid:8050349

only dendritic cells presented to cd8  T cells (not the macrophages)
https://www.ncbi.nlm.nih.gov/pubmed/11828323/

memory B cells are reactivated by scs macophages
https://www.nature.com/articles/s41467-018-05772-7

SCS is the subcapular sinus macrophage

Marginal zone B cells shuttle antigens to FDC
https://www.ncbi.nlm.nih.gov/pubmed/18037889

Langerhans promotes the GC-B/Tfh formation during a leishmania infection
https://www.ncbi.nlm.nih.gov/pubmed/25070244

Possible that langerhans shuttles antigens like MZ B cells

Contemplations of IgG2 and IgG3 antibodies

When it comes to viruses IgG2 binds cytosolic viruses and IgG3 binds mitochondrial and nuclear viruses but what happens when bacterias and parasites move inside of the host cell? Which IgG antibodies are involved?

Cytosol infections : mycobacteria and fungus

IgG2 and mycobacteria
https://cvi.asm.org/content/10/1/88

IgG2 and cryptococcus
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828574/

cryptococcus neuformans (fungus) in the cytosol of cells
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127716/

IgG3 and bacteria? complement?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979173/

Vacuole/golgi bacteria or parasites hypothesis involves TH17 il-22 or il-24 to pop them and does this involve IgG3?

il-17 and il-22 with leishmaniasis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2719936/

IgG3 and il-10 with leishmaniasis

plasmacytoid dendritic cells and leishmaniasis ?
https://www.ncbi.nlm.nih.gov/pubmed/17705130

IgG3 and listeria
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC201853/

listeria and vacuoles
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006734

pDendritic cells and listeria ?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078036/


IgG3 and Follicular dendritic cells
https://www.nature.com/articles/s41598-017-05704-3

This would loop back to the outside antigens (after the bacteria was released from internal regions and allow Somatic hypermutation against the now visible bacteria/parasite)

IgG3 complexes are bound by Neutrophils 3x faster than IgG1
https://www.ncbi.nlm.nih.gov/pubmed/2784461

note that il-17A calls neutrophils
https://www.nature.com/articles/mi201680

LEC educates on local antigens before allowing cells into lymph gland

LEC educates on local antigens before allowing cells into lymph gland

Tolerance is the "self education" given the B and T cells. B cells have been taught the external antigens in the bone marrow while T cells have learned the internal DNA/RNA antigens in the thymus. These self educations where all genes are expressed are called Central Tolerance.

Peripheral Tolerance is given to B and T cells by the gatekeeper cells of the lymph glands: the Lymphatic Endothelial cells.  Lymphatic endothelial cells express the tissue specific genes of the cells of their area. They also sample and wear the antigens commonly found in their area.

These lymphatic endothelial cells will only allow in T and B cells that do not react with the self antigens specific to the tissues of the of the peripheral area into the lymph gland.  (B cells are hypothesized to be educated too but this is not proven)

Current ideology is that if we can get antigens from a transplanted organ into the LEC tolerance to the transplanted organ will occur. The question is how is this done exactly and how often do LEC update their antigens.

lymphatic endothelial cells
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226940/

bone marrow cells
http://www.jimmunol.org/content/196/1_Supplement/55.28

VEC and BEC express their areas antigens
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2137938/

LEC have mhc1 and mhc2
https://www.jci.org/articles/view/73316