scholarly journals Developmentally regulated association of a 56-kD member of the surface immunoglobulin M receptor complex.

1992 ◽  
Vol 176 (1) ◽  
pp. 129-137 ◽  
Author(s):  
A J Yellen-Shaw ◽  
J G Monroe
Keyword(s):  
B Cells ◽  
Antigen Receptor ◽  
Immature Stage ◽  
Developmental Differences ◽  
Immunoglobulin M ◽  
Receptor Complex ◽  
Developmentally Regulated ◽  
Two Dimensional Gel Electrophoresis ◽  
Surface Immunoglobulin ◽  
Stage Of Development

Immature and mature B cells differ in the signals generated and transduced through their antigen receptor, surface immunoglobulin M (sIgM). Whereas signals generated through sIgM on mature B cells initiate a program leading to the positive activation of these cells, signaling through this receptor at the immature stage of development leads to a state of induced unresponsiveness or tolerance. Our previous studies have described developmental differences in sIgM transmembrane signaling that are independent of ligand-receptor affinity. In an attempt to understand the molecular basis for signaling differences between immature and mature B cells, we have analyzed the sIgM receptor complex in neonatal and adult mouse splenic B cells. While previously described components of this complex do not exhibit marked developmentally regulated differences in their association with sIgM, we have identified a 56-kD protein that associates with sIgM in mature (antigen-responsive), but not immature (tolerance-sensitive) B cells. This protein (p56) associates with sIgM as a homodimer, is constitutively phosphorylated on tyrosine, and is coimmunoprecipitated with IgM but not IgD. The observed inability to iodinate p56 suggests it is an intracellular component of the receptor complex. Based upon its migration in one- and two-dimensional gel electrophoresis we show, however, that p56 is distinct from the blk, lyn, or fyn src family kinases that have been shown to be associated with sIgM in mature B cells. The developmentally regulated participation of p56 in the B cell antigen receptor complex suggests a role in the differential signaling mediated via sIgM on immature and mature B cells.

scholarly journals Immunoglobulin gene rearrangements in normal mouse B cells

1982 ◽  
Vol 2 (7) ◽  
pp. 829-836
Author(s):  
P Early ◽  
C Nottenburg ◽  
I Weissman ◽  
L Hood
Keyword(s):  
B Cells ◽  
Heavy Chain ◽  
Germ Line ◽  
Gene Segment ◽  
Immunoglobulin M ◽  
Chain Gene ◽  
Allelic Exclusion ◽  
Immunoglobulin Gene ◽  
Spleen Cells ◽  
Surface Immunoglobulin

We have analyzed the structure of rearranged mu heavy-chain genes obtained from the genomic DNA of normal BALB/c mouse spleen cells expressing surface immunoglobulin M. Examples were found of two types of nonproductive rearrangements, which may be responsible for allelic exclusion in normal B cells. In one of these rearrangements, a germ line D gene segment has joined to the JH4 gene segment but no V/D joining has occurred. We present evidence that D gene segments lie as a cluster between V and J gene segments in the germ line. A comparison of conserved sequences in V and D gene segments suggests that the D gene segments, which are found only in the heavy-chain gene family, may have evolved from V gene segments similar to the Vk family.

scholarly journals Pre-B and B cells in rabbits. Ontogeny and allelic exclusion of kappa light chain genes.

1978 ◽  
Vol 148 (5) ◽  
pp. 1367-1377 ◽  
Author(s):  
A R Hayward ◽  
M A Simons ◽  
A R Lawton ◽  
R G Mage ◽  
M D Cooper
Keyword(s):  
B Cells ◽  
B Lymphocytes ◽  
Early Stage ◽  
Fetal Liver ◽  
General Pattern ◽  
Allelic Exclusion ◽  
Kappa Light Chain ◽  
Surface Immunoglobulin ◽  
Stage Of Development ◽  
Adult Bone

Pre-B cells in developing rabbits were identified by immunofluorescence as cells containing small amounts of cytoplasmic IgM (cIgM) but lacking surface immunoglobulin (sIg). During ontogeny the first pre-B cells appeared in fetal liver at 23 days gestation, 2 days before the appearance of sIgM+ B lymphocytes. Pre-B cells were relatively frequent in fetal and adult bone marrow, but were not found in other tissues except rarely in fetal spleen. Allelic exclusion is apparently established at this early stage of development, because individual pre-B cells and B lymphocytes from heterozygous rabbits expressed only one of the alternative alleles in amounts sufficient for detection. Development of isotype diversity among rabbit B lymphocytes followed the general pattern seen in mouse and man. sIgM+ cells were detected before birth. Expression of sIgG was detected in neonatal rabbits on cells which were also sIgM+ but in older animals most sIgG+ cells lacked sIgM. Cells bearing sIgA were not found until 5-6 days of age, and had no other isotype on their surface.

scholarly journals A Novel B Lymphocyte–Associated Adaptor Protein, Bam32, Regulates Antigen Receptor Signaling Downstream of Phosphatidylinositol 3-Kinase

2000 ◽  
Vol 191 (8) ◽  
pp. 1319-1332 ◽  
Author(s):  
Aaron J. Marshall ◽  
Hiroaki Niiro ◽  
Cara G. Lerner ◽  
Theodore J. Yun ◽  
Sushma Thomas ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Antigen Receptor ◽  
Adaptor Protein ◽  
Immunoglobulin M ◽  
Binding Motif ◽  
Ph Domain ◽  
Phosphatidylinositol 3 Kinase ◽  
Activated T Cells ◽  
Phosphatidylinositol 3

We have identified and characterized a novel src homology 2 (SH2) and pleckstrin homology (PH) domain–containing adaptor protein, designated Bam32 (for B cell adaptor molecule of 32 kD). cDNAs encoding the human and mouse Bam32 coding sequences were isolated and the human bam32 gene was mapped to chromosome 4q25–q27. Bam32 is expressed by B lymphocytes, but not T lymphocytes or nonhematopoietic cells. Human germinal center B cells show increased Bam32 expression, and resting B cells rapidly upregulate expression of Bam32 after ligation of CD40, but not immunoglobulin M. Bam32 is tyrosine-phosphorylated upon B cell antigen receptor (BCR) ligation or pervanadate stimulation and associates with phospholipase Cγ2. After BCR ligation, Bam32 is recruited to the plasma membrane through its PH domain. Membrane recruitment requires phosphatidylinositol 3-kinase (PI3K) activity and an intact PI(3,4,5)P3-binding motif, suggesting that membrane association occurs through binding to 3-phosphoinositides. Expression of Bam32 in B cells leads to a dose-dependent inhibition of BCR-induced activation of nuclear factor of activated T cells (NF-AT), which is blocked by deletion of the PH domain or mutation of the PI(3,4,5)P3-binding motif. Thus, Bam32 represents a novel B cell–associated adaptor that regulates BCR signaling downstream of PI3K.

scholarly journals Human interleukin 10 induces naive surface immunoglobulin D+ (sIgD+) B cells to secrete IgG1 and IgG3.

1994 ◽  
Vol 179 (2) ◽  
pp. 757-762 ◽  
Author(s):  
F Brière ◽  
C Servet-Delprat ◽  
J M Bridon ◽  
J M Saint-Remy ◽  
J Banchereau
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
Interleukin 10 ◽  
Immunoglobulin M ◽  
Surface Immunoglobulin ◽  
Human B Cells ◽  
Immunoglobulin D ◽  
Switch Factor ◽  
Hyper Igm ◽  
Growth Promoting

During antigen-induced immune responses, human B cells switch isotype from immunoglobulin M (IgM)-IgD to IgG1-4, IgA1-2, or IgE. In the human, no cytokines have yet been demonstrated to act as switch factors for IgG1, IgG2, and IgG3. In this paper, we report that in response to interleukin 10 (IL-10), anti-CD40 activated tonsillar surface IgD+ (sIgD+) B cells are induced to secrete large amounts of IgM, IgG1, and IgG3 but neither IgG2 nor IgG4. Cord blood purified B cells and lymphocytes from Hyper-IgM patients also produced IgG1 and IgG3 after culture with anti-CD40 and IL-10. In contrast, sIgD- isotype-committed B cells produce IgG1, IgG2, and IgG3 when activated through CD40 in the presence of IL-10. Thus, in addition to its growth-promoting and differentiating activities on human B cells, IL-10 may represent a switch factor for IgG1 and IgG3.

scholarly journals EVENTS AFTER THE BINDING OF ANTIGEN TO LYMPHOCYTES

1974 ◽  
Vol 139 (5) ◽  
pp. 1110-1124 ◽  
Author(s):  
Kenneth A. Ault ◽  
Emil R. Unanue
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Prolonged Exposure ◽  
Specific Antigen ◽  
Antigen Receptor ◽  
Keyhole Limpet Hemocyanin ◽  
Antigen Binding ◽  
Inhibition Assay ◽  
Rapid Loss ◽  
Surface Immunoglobulin

The behavior of the immunoglobulin antigen receptor on lymphocytes was studied using both fluorescent antiimmunoglobulin antibody to detect B cells and autoradiography with radiolabeled antigens to detect antigen-binding cells. It was shown that after binding of antiimmunoglobulin antibody to the lymphocyte there was a rapid loss of surface immunoglobulin and then a progressive reappearance over 18 h. This could be quantitated using an inhibition assay for surface immunoglobulin. Similarly, after binding various dinitrophenyl-conjugated proteins or keyhole limpet hemocyanin to their specific antigen-binding cells, there was a loss of the antigen receptor from the surface and then a progressive reappearance of the receptor. The reappearance of surface immunoglobulin and of the antigen receptor proceeded at about the same rate. Repeated exposure to antibody or prolonged exposure to antigen did not diminish the capacity of the lymphocyte to re-express its receptor. These events, which follow the interaction of antigen and its receptor, are of possible importance in understanding the mechanism of triggering of the immune response and of tolerance.

scholarly journals Activation mediated by RP105 but not CD40 makes normal B cells susceptible to anti-IgM-induced apoptosis: a role for Fc receptor coligation.

1996 ◽  
Vol 184 (1) ◽  
pp. 113-120 ◽  
Author(s):  
Y Yamashita ◽  
K Miyake ◽  
Y Miura ◽  
Y Kaneko ◽  
H Yagita ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Great Influence ◽  
Antigen Receptor ◽  
Immunoglobulin M ◽  
Cd40 Ligation ◽  
Cell Surface Molecule ◽  
Blast Cells ◽  
Induced Apoptosis ◽  
Activated B Cells

Signals through the B cell antigen receptor lead to a variety of cellular events such as activation, anergy, and apoptosis. B cells select these outcomes to establish and maintain self-tolerance, and to mount adequate antibody responses. However, it is not fully understood how one and the same signal causes such different consequences. In the present study, we have studied the effect of activation signals on the outcome of responses to antigen receptor ligation. Two distinct growth-promoting signals were used to activate B cells. Ligation of either RP105, a newly discovered B cell surface molecule, or the CD40 molecule, drove B cells to proliferate. Resultant blastic cells were then exposed to anti-immunoglobulin M (IgM). Blast cells that had been stimulated with anti-RP105 ceased growing and underwent apoptosis after cross-linking of surface IgM. Coligation of the Fc gamma receptor IIB with surface IgM augmented, rather than aborted, this response. In contrast to RP105-activated B cells, blast cells that had been activated by CD40 ligation were unaltered by anti-IgM. On the other hand, CD40-activated B cells became extremely susceptible to Fas-mediated apoptosis, whereas RP105-activated B cells were much less sensitive. Anti-IgM-induced apoptosis in RP105 blasts was independent of Fas, because it was demonstrable with Fas-deficient MRL-lpr/lpr mice. These results demonstrate that the nature of an initial activation signal has a great influence on the fate of activated B cells after (re)engagement of the antigen receptor. RP105, as well as CD40, may be important in this life/death decision.

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