scholarly journals Faculty Opinions recommendation of Intrathymic differentiation of natural antibody-producing plasma cells in human neonates.

Author(s):  
Elizabeth Mellins ◽  
Debopam Ghosh
immuneACCESS ◽  
2021 ◽  
Author(s):  
H Cordero ◽  
RG King ◽  
P Dogra ◽  
C Dufeu ◽  
SB See ◽  
...  

2020 ◽  
Author(s):  
Hector Cordero ◽  
Rodney King ◽  
Pranay Dogra ◽  
Chloe Dufeu ◽  
Sarah See ◽  
...  

Abstract The thymus is a central lymphoid organ responsible for the development of T cells. Here, we show that the thymus of human neonates also contains a consistent contingent of CD138+ plasma cells, producing all classes and subclasses of immunoglobulins with the exception of IgD. These antibody-secreting cells (ASC) are comprised within a larger subset of B cells lacking expression of the complement receptors CD21 and CD35 and sharing the expression of signature genes defining mouse B1 B cells. Single-cell transcriptomic analyses supported the intrathymic differentiation of CD138+ plasma cells alongside other B cell subsets with distinctive molecular phenotypes. Neonatal thymic plasma cells also included clones reactive to pathogenic bacteria that commonly infect children born with antibody deficiency. Thus, our findings point to the thymus as a source of innate humoral immunity in human neonates.


2008 ◽  
Vol 105 (40) ◽  
pp. 15517-15522 ◽  
Author(s):  
Jean L. Scholz ◽  
Jenni E. Crowley ◽  
Mary M. Tomayko ◽  
Natalie Steinel ◽  
Patrick J. O'Neill ◽  
...  

We have used an inhibiting antibody to determine whether preimmune versus antigen-experienced B cells differ in their requisites for BLyS, a cytokine that controls differentiation and survival. Whereas in vivo BLyS inhibition profoundly reduced naïve B cell numbers and primary immune responses, it had a markedly smaller effect on memory B cells and long-lived plasma cells, as well as secondary immune responses. There was heterogeneity within the memory pools, because IgM-bearing memory cells were sensitive to BLyS depletion whereas IgG-bearing memory cells were not, although both were more resistant than naïve cells. There was also heterogeneity within B1 pools, as splenic but not peritoneal B1 cells were diminished by anti-BLyS treatment, yet the number of natural antibody-secreting cells remained constant. Together, these findings show that memory B cells and natural antibody-secreting cells are BLyS-independent and suggest that these pools can be separately manipulated.


2017 ◽  
Vol 214 (9) ◽  
pp. 2777-2794 ◽  
Author(s):  
Hannah P. Savage ◽  
Vanessa M. Yenson ◽  
Sanjam S. Sawhney ◽  
Betty J. Mousseau ◽  
Frances E. Lund ◽  
...  

Natural antibodies contribute to tissue homeostasis and protect against infections. They are secreted constitutively without external antigenic stimulation. The differentiation state and regulatory pathways that enable continuous natural antibody production by B-1 cells, the main cellular source in mice, remain incompletely understood. Here we demonstrate that natural IgM-secreting B-1 cells in the spleen and bone marrow are heterogeneous, consisting of (a) terminally differentiated B-1–derived plasma cells expressing the transcriptional regulator of differentiation, Blimp-1, (b) Blimp-1+, and (c) Blimp-1neg phenotypic B-1 cells. Blimp-1neg IgM-secreting B-1 cells are not simply intermediates of cellular differentiation. Instead, they secrete similar amounts of IgM in wild-type and Blimp-1–deficient (PRDM-1ΔEx1A) mice. Blimp-1neg B-1 cells are also a major source of IgG3. Consequently, deletion of Blimp-1 changes neither serum IgG3 levels nor the amount of IgG3 secreted per cell. Thus, the pool of natural antibody-secreting B-1 cells is heterogeneous and contains a distinct subset of cells that do not use Blimp-1 for initiation or maximal antibody secretion.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hector Cordero ◽  
Rodney G. King ◽  
Pranay Dogra ◽  
Chloe Dufeu ◽  
Sarah B. See ◽  
...  

AbstractThe thymus is a central lymphoid organ primarily responsible for the development of T cells. A small proportion of B cells, however, also reside in the thymus to assist negative selection of self-reactive T cells. Here we show that the thymus of human neonates contains a consistent contingent of CD138+ plasma cells, producing all classes and subclasses of immunoglobulins with the exception of IgD. These antibody-secreting cells are part of a larger subset of B cells that share the expression of signature genes defining mouse B1 cells, yet lack the expression of complement receptors CD21 and CD35. Data from single-cell transcriptomic, clonal correspondence and in vitro differentiation assays support the notion of intrathymic CD138+ plasma cell differentiation, alongside other B cell subsets with distinctive molecular phenotypes. Lastly, neonatal thymic plasma cells also include clones reactive to commensal and pathogenic bacteria that commonly infect children born with antibody deficiency. Thus, our findings point to the thymus as a source of innate humoral immunity in human neonates.


Author(s):  
Dale E. Bockman ◽  
L. Y. Frank Wu ◽  
Alexander R. Lawton ◽  
Max D. Cooper

B-lymphocytes normally synthesize small amounts of immunoglobulin, some of which is incorporated into the cell membrane where it serves as receptor of antigen. These cells, on contact with specific antigen, proliferate and differentiate to plasma cells which synthesize and secrete large quantities of immunoglobulin. The two stages of differentiation of this cell line (generation of B-lymphocytes and antigen-driven maturation to plasma cells) are clearly separable during ontogeny and in some immune deficiency diseases. The present report describes morphologic aberrations of B-lymphocytes in two diseases in which second stage differentiation is defective.


Author(s):  
Hannah R. Brown ◽  
Tammy L. Donato ◽  
Halldor Thormar

Measles virus specific immunoglobulin G (IgG) has been found in the brains of patients with subacute sclerosing panencephalitis (SSPE), a slowly progressing disease of the central nervous system (CNS) in children. IgG/albumin ratios indicate that the antibodies are synthesized within the CNS. Using the ferret as an animal model to study the disease, we have been attempting to localize the Ig's in the brains of animals inoculated with a cell associated strain of SSPE. In an earlier report, preliminary results using Protein A conjugated to horseradish peroxidase (PrAPx) (Dynatech Diagnostics Inc., South Windham, ME.) to detect antibodies revealed the presence of immunoglobulin mainly in antibody-producing plasma cells in inflammatory lesions and not in infected brain cells.In the present experiment we studied the brain of an SSPE ferret with neutralizing antibody titers of 1:1024 in serum and 1:512 in CSF at time of sacrifice 7 months after i.c. inoculation with SSPE measles virus-infected cells. The animal was perfused with saline and portions of the brain and spinal cord were immersed in periodate-lysine-paraformaldehyde (P-L-P) fixative. The ferret was not perfused with fixative because parts of the brain were used for virus isolation.


Author(s):  
Amreek Singh ◽  
Judith M. McLaren ◽  
Onkar S. Atwal ◽  
Peter Eyre

Introduction3-methylindole (MI), a rumen metabolite of the amino acid L-tryptophan, has been shown to produce bovine pulmonary edema and emphysema. The airways contain free and exfoliated cells. A morphologic analysis of these cells may complement the understanding of the mechanism of lung edema. Ultrastructure of the bronchopulmonary lavage (BL) cells 24 h following MI oral administration to calves is described in this experiment. The 12 hours post-treatment results were described earlier.Materials and MethodsTwo Holstein-Friesian calves were each administered an oral dose of 0.2 g MI/Kg body weight and another two calves served as controls. The animals were euthanized with sodium pentabarbitol 24 h after receiving the compound. The lungs and trachea were removed and 0.1 M sodium phosphate buffered saline was infused into the lungs through the trachea. Glutaraldehyde fixative was added to the recovered BL fluid so as to form a 1% solution. The fluid was centrifuged and the resulting cell pellet was suspended in the buffer. The procedures were repeated on the suspension; the pellet was post-fixed in osmium tetroxide and was processed by conventional methods of section preparations for TEM examination. Lung samples from caudal lobes were fixed in 1.5% glutaraldehyde to obtain tissue sections for TEM.Results and DiscussionPulmonary alveolar macrophages (AM), neutrophils, ciliated epithelial cells, globule leukocytes and plasma cells were recovered from the BL fluid of the control and Mi-administered calves. Ciliated cells and globule leukocytes could not be harvested from the controls. The AM obtained from the treated calves (Fig. 1) in comparison with similar cells from the controls were larger, and contained large membrane-limited inclusions (phagolysosomes). There was a remarkable similarity between the lavaged AM and the AM studied in thin sections of lung (cf. Fig. 1 and Fig. 2). The neutrophil was the second most abundant cell type retrieved from the lavage fluid from the calves of control or treated group. Except for scanty pseudopodia in the neutrophils obtained from the Mi-receiving calves, the cells appeared unaltered (Fig. 3). Ciliated cells were abundant in the BL fluid of Mi-ingesting calves. A heterogeneous collection of vesicles filled the ciliated cell cytoplasm (Fig. 3). Globule leukocytes were commonly observed among BL cells of treated calves. The globule leukocytes were ca. 15 μm in diameter and contained round or elliptical nuclei with conspicuous nucleoli. The cytoplasmic granules, which are a prominent feature of globule leukocytes, were electron-opaque and had a variable diameter (0.5-3.0 μm). A one-line account of globule leukocytes in the bronchi of steers administered MI has appeared. Plasma cells were rare. Ultrastructure of BL cells is compatible with their response to chemical insult by MI.


Author(s):  
S.L. Asa ◽  
K. Kovacs ◽  
J. M. Bilbao ◽  
R. G. Josse ◽  
K. Kreines

Seven cases of lymphocytic hypophysitis in women have been reported previously in association with various degrees of hypopituitarism. We report two pregnant patients who presented with mass lesions of the sella turcica, clinically mimicking pituitary adenoma. However, pathologic examination revealed extensive infiltration of the anterior pituitary by lymphocytes and plasma cells with destruction of the gland. To our knowledge, the ultrastructural features of lymphocytic hypophysitis have not been studied so far.For transmission electron microscopy, tissue from surgical specimens was fixed in glutaraldehyde, postfixed in OsO4, dehydrated and embedded in epoxy-resin. Ultrathin sections were stained with uranyl acetate and lead citrate and examined with a Philips 300 electron microscope.Electron microscopy revealed adenohypophysial cells of all types exhibiting varying degrees of injury. In the areas of most dense inflammatory cell infiltration pituitary cells contained large lysosomal bodies fusing with secretory granules (Fig. 1), as well as increased numbers of swollen mitochondria, indicating oncocytic transformation (Fig. 2).


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