Figure 1111

Central role of T cells specific for nucleosomal histone peptides in the generation of the antinuclear autoantibody repertoire in systemic lupus erythematosus. The cascade begins with the uptake of nucleosomes by B cells by way of their antigen receptor. After endosomal antigen processing, these B cells present histone peptides to T cells. After activation of the T cell, it provides help to the presenting B cell, leading to the formation of nucleosome-specific autoantibodies. Binding of B cells to other determinants on the nucleosome (B cells specific for DNA, histones, or the nonhistone chromosomal peptides high-mobility group proteins [HMG]) and antigen-processing by these B cells, can generate additional antinuclear autoantibody responses (anti-doubled-stranded DNA, antihis-tone, and anti-HMG). This intramolecular antigen-spreading owing to different endosomal antigen-processing revealing cryptic neoepi-topes, is now known for a number of autoimmune responses [44]. MHC—major histocompatibility complex; TCR—T-cell receptor. (From Datta and Kaliyaperumal [45]; with permission.)



I. Normal glomeruli

A. Nil (by all techniques)

B. Normal on light microscopy but deposits seen on electron or immunofluores-cence microscopy

II. Pure mesangial alterations (mesangiopathy)

A. Mesangial widening, mild hypercellularity, or both

B. Moderate hypercellularity

III. Focal segmental glomerulonephritis (associated with mild or moderate mesangial alterations)

A. Active necrotizing lesions

B. Active and sclerosing lesions

C. Sclerosing lesions

IV. Diffuse glomerulonephritis (Severe mesangial, endocapillary, or mesangiocapillary proliferation, and/or extensive subendothelial deposits. Mesangial deposits are present invariably and subepithelial deposits often, and may be numerous.)

A. Without segmental lesions

B. With active necrotizing lesions

C. With active and sclerosing lesions

D. With sclerosing lesions

V. Diffuse membranous glomerulonephritis

A. Pure membranous glomerulonephritis

B. Associated with lesions of category II (A or B)

VI. Advanced sclerosing glomerulonephritis

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