Clin Exp Rheumatol. 2015 Jul-Aug;33(4 Suppl 92):S80-6. Epub 2015 Oct 12.

Selection of natural autoreactive B cells.

Hardy RR1, Hayakawa K2.

Author information

Abstract

Natural antibodies produced by CD5+ B1 B cells include anti-thymocyte autoantibody (ATA). Transgenic mice bearing the Ig-μ heavy chain of a prototypic ATA, V(H)3609Vκ21c, demonstrated a critical requirement for self-antigen in the accumulation of ATA B cells and production of high levels of serum ATA. Further work with ATA-μκ transgenic mice revealed that, while development of most B cells were blocked at an immature stage in spleen, some mature ATA B cells were present. ATA-μκ transgenic mice with varying levels of Thy-1 autoantigen showed a clear relationship between BCR crosslinking and B cell fate, with low levels generating marginal zone ATA B cells and complete antigen absence allowing maturation to follicular ATA B cells. Finally, different fates of developing ATA B cells encountering high levels self-antigen may be accounted for by variations in the response of newly formed B cells arising from foetal and adult development.

PMID:

26457505

[PubMed - indexed for MEDLINE]

Adv Exp Med Biol. 2012;750:227-38. doi: 10.1007/978-1-4614-3461-0_17.

Positive and negative selection of natural autoreactive B cells.

Hardy RR1, Hayakawa K.

Author information

Abstract

Naturally occurring antibodies (NAbs) produced by CD5(+) B-1 B cells include those with specificity for thymocytes (anti-thymocyte autoantibody, ATA). Here we describe a prototypic example, encoded by an unmutated immunoglobulin μ/κ heavy chain/light chain. Studies with ATA-μ ("heavy chain only") transgenic mice demonstrated a critical requirement for self-antigen in the accumulation of B cells with this specificity and for the production of high levels of serum ATA NAb. Furthermore, analysis of B-cell development in ATA-μκ ("heavy and light chain") transgenic mice revealed two distinct responses by B cells to expression of this B-cell receptor (BCR). (1) Most B cells developing from bone marrow of adult mice were blocked at an immature stage in spleen and only escaped apoptosis by editing their BCR to eliminate the ATA specificity. (2) Some B cells differentiated to antibody-forming cells without altering their specificity, produced high levels of serum ATA, and many ATA-secreting plasma cells were observed in spleen. Finally, examination of B-cell development and ATA NAb production in ATA-μκ transgenic mice with levels of Thy-1 autoantigen varying from very low to above physiologic reveals a clear relationship between BCR crosslinking by antigen and B-cell fate. Low levels of Thy-1 autoantigen resulted in diversion of ATA B cells into the marginal zone B-cell compartment, presumably because of reduced BCR signaling. Thus, our studies demonstrate a key positive selection step in the development of NAb-producing B cells and show that most of these cells in adult mice bearing such specificities fail to reach a mature stage. Importantly, because these specificities are isolated from B-1 B cells and, when expressed as transgenes, guide development into the B-1 or marginal zone B-cell pool, we identify these B cells as a major source of natural autoantibodies in mice.

PMID:

22903678

[PubMed - indexed for MEDLINE]

Thank you Dr. Tuzun.  I appreciate the information.

You can use PHA or PMA with ionomycin to uprwgulate CD5 cells but that will affect the differentiation of your T cells also. You can find more info on my paper of CD5 and HCV.

Thank you Dr. Sarhan,

Could you please direct me to your paper on CD5 and HCV?

https://www.researchgate.net/publication/221778296_Hepatitis_C_Virus_Infection_of_Human_T_Lymphocytes_Is_Mediated_by_CD5?ev=prf_pub

Article Hepatitis C Virus Infection of Human T Lymphocytes Is Mediated by CD5