Question

Please draw a figure that represents the role of B cells in the autoimmune disease: Systemic lupus erythematous

Answer 1

Figure Representation:

Central tolerance.

1, Common lymphocyte precursor commits to B cell lineage via expression of B cell–specific transcription factors (e.g., early B cell factor [EBF]), which initiates IgH rearrangement.

2, Expression of the generated IgH component of the pre–B cell receptor (pre‐BCR) is combined with the surrogate light chain (SLC).

3, Successful signaling through the pre‐BCR leads to a short burst of proliferation and internalization of the pre‐BCR and commences a second wave of recombination, this time in the light‐chain gene.

4, The generated BCR is then assessed for self‐recognition. Those cells that have generated non–self‐recognizing BCRs with functioning signaling switch off recombination‐activating gene (RAG) expression and become immature B cells.

5, Because V[D]J recombination is a stochastic process, a proportion of pre–B cells will generate autoreactive BCRs. This is detected by excess BCR signaling due to high‐affinity binding within the bone marrow or abundance of antigen. This leads to continued V[D]J recombination until acceptable BCR is generated or all possible recombination has been exhausted.

6, Failure to generate a non–self‐recognizing BCR leads to apoptosis.

7, In autoimmune disease this process is impaired, potentially by reduced signaling through the developing BCR, which fails to trigger the threshold for apoptosis. Genes or proteins involved at each stage are shown in dashed boxes.

* = genes identified as risk‐associated loci in systemic lupus erythematosus (SLE). TLR = Toll‐like receptor; MyD88 = myeloid differentiation factor 88; IRAK‐1 = interleukin‐1 receptor–associated kinase 1; Unc‐93B = Unc‐93 homolog B